{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:47:56Z","timestamp":1792003676433,"version":"4.4.0"},"reference-count":274,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["5R01AI141801-04"],"award-info":[{"award-number":["5R01AI141801-04"]}]},{"name":"NIH","award":["1R01AI65876-01"],"award-info":[{"award-number":["1R01AI65876-01"]}]},{"name":"NIH","award":["FP15713"],"award-info":[{"award-number":["FP15713"]}]},{"name":"Zoetis","award":["5R01AI141801-04"],"award-info":[{"award-number":["5R01AI141801-04"]}]},{"name":"Zoetis","award":["1R01AI65876-01"],"award-info":[{"award-number":["1R01AI65876-01"]}]},{"name":"Zoetis","award":["FP15713"],"award-info":[{"award-number":["FP15713"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The acceleration of climate change has been associated with an alarming increase in the prevalence and geographic range of tick-borne diseases (TBD), many of which have severe and long-lasting effects\u2014particularly when treatment is delayed principally due to inadequate diagnostics and lack of physician suspicion. Moreover, there is a paucity of treatment options for many TBDs that are complicated by diagnostic limitations for correctly identifying the offending pathogens. This review will focus on the biology, disease pathology, and detection methodologies used for the Borreliaceae family which includes the Lyme disease agent Borreliella burgdorferi. Previous work revealed that Borreliaceae genomes differ from most bacteria in that they are composed of large numbers of replicons, both linear and circular, with the main chromosome being the linear with telomeric-like termini. While these findings are novel, additional gene-specific analyses of each class of these multiple replicons are needed to better understand their respective roles in metabolism and pathogenesis of these enigmatic spirochetes. Historically, such studies were challenging due to a dearth of both analytic tools and a sufficient number of high-fidelity genomes among the various taxa within this family as a whole to provide for discriminative and functional genomic studies. Recent advances in long-read whole-genome sequencing, comparative genomics, and machine-learning have provided the tools to better understand the fundamental biology and phylogeny of these genomically-complex pathogens while also providing the data for the development of improved diagnostics and therapeutics.<\/jats:p>","DOI":"10.3390\/genes13091604","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T07:05:56Z","timestamp":1662620756000},"page":"1604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Large-Scale Sequencing of Borreliaceae for the Construction of Pan-Genomic-Based Diagnostics"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-2248","authenticated-orcid":false,"given":"Kayla M.","family":"Socarras","sequence":"first","affiliation":[{"name":"Center for Advanced Microbial Processing, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Genomic Sciences, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-0759","authenticated-orcid":false,"given":"Benjamin S.","family":"Haslund-Gourley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, 1112 East Clay Street, Room 101 Health Sciences Research Building, Richmond, VA 23298, USA"},{"name":"Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ann","family":"Comunale","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-7306","authenticated-orcid":false,"given":"Richard T.","family":"Marconi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, 1112 East Clay Street, Room 101 Health Sciences Research Building, Richmond, VA 23298, USA"},{"name":"Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth D.","family":"Ehrlich","sequence":"additional","affiliation":[{"name":"Center for Advanced Microbial Processing, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Center for Genomic Sciences, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"},{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, 1112 East Clay Street, Room 101 Health Sciences Research Building, Richmond, VA 23298, USA"},{"name":"Center for Surgical Infections and Biofilms, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gubler, D.J. (2013). Arthropods in Disease Transmission. Hunter\u2019s Tropical Medicine and Emerging Infectious Disease, Saunders.","DOI":"10.1016\/B978-1-4160-4390-4.00141-7"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.idc.2007.12.006","article-title":"Biology of Ticks","volume":"22","author":"Anderson","year":"2008","journal-title":"Infect. Dis. Clin. North Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0025-7125(03)00083-X","article-title":"The Natural History of Ticks","volume":"86","author":"Anderson","year":"2002","journal-title":"Med. Clin. North Am."},{"key":"ref_4","unstructured":"Obenchain, F.D., and Galun, R. (2013). Physiology of Ticks: Current Themes in Tropical Science, Elsevier."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Smith, T., and Kilborne, F.L. (1893). Investigations into the Nature, Causation, and Prevention of Texas Or Southern Cattle Fever.","DOI":"10.5962\/bhl.title.124068"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/jme\/tjab064","article-title":"The Rise of Ticks and Tickborne Diseases in the United States-Introduction","volume":"58","author":"Beard","year":"2021","journal-title":"J. Med. Entomol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1128\/CMR.18.3.484-509.2005","article-title":"Diagnosis of Lyme Borreliosis","volume":"18","author":"Wang","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mosel, M.R., Aucott, J., Schutzer, S.E., Marques, A., Arnaboldi, P.M., Dattwyler, R., and Eshoo, M.W. (2021). Lyme Disease Diagnostics. Lyme Disease and Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions and Disease Pathogenesis 2021, Caister Academic Press.","DOI":"10.21775\/9781913652616.22"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bowman, A.S., and Nuttall, P.A. (2008). Ticks: Biology, Disease and Control, Cambridge University Press.","DOI":"10.1017\/CBO9780511551802"},{"key":"ref_10","unstructured":"(1908). Entomological Society of America Bloodsucking Ticks (Ixodoidea)\u2014Vectors of Diseases of Man and Animals\u2014Translated From Russia, Entomological Society of America."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1111\/evo.12690","article-title":"Recent and Rapid Population Growth and Range Expansion of the Lyme Disease Tick Vector, Ixodes Scapularis, in North America","volume":"69","author":"Khatchikian","year":"2015","journal-title":"Evolution"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1365-2664.2012.02112.x","article-title":"Predicting the Speed of Tick Invasion: An Empirical Model of Range Expansion for the Lyme Disease vectorIxodes Scapularisin Canada","volume":"49","author":"Leighton","year":"2012","journal-title":"J. Appl. Ecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ijpara.2005.08.016","article-title":"Climate Change and the Potential for Range Expansion of the Lyme Disease Vector Ixodes Scapularis in Canada","volume":"36","author":"Ogden","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1476-072X-7-24","article-title":"Risk Maps for Range Expansion of the Lyme Disease Vector, Ixodes Scapularis, in Canada Now and with Climate Change","volume":"7","author":"Ogden","year":"2008","journal-title":"Int. J. Health Geogr."},{"key":"ref_15","first-page":"20202278","article-title":"Landscape Features Predict the Current and Forecast the Future Geographic Spread of Lyme Disease","volume":"287","author":"Gardner","year":"2020","journal-title":"Proc. Biol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/jme\/tjv237","article-title":"County-Scale Distribution of Ixodes Scapularis and Ixodes Pacificus (Acari: Ixodidae) in the Continental United States","volume":"53","author":"Eisen","year":"2016","journal-title":"J. Med. Entomol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"237","DOI":"10.4269\/ajtmh.1995.53.237","article-title":"Evidence Implicating Nymphal Ixodes Pacificus (Acari: Ixodidae) in the Epidemiology of Lyme Disease in California","volume":"53","author":"Clover","year":"1995","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sonenshine, D.E. (2018). Range Expansion of Tick Disease Vectors in North America: Implications for Spread of Tick-Borne Disease. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15030478"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1093\/jme\/tjw076","article-title":"Modeling the Geographic Distribution of Ixodes Scapularis and Ixodes Pacificus (Acari: Ixodidae) in the Contiguous United States","volume":"53","author":"Hahn","year":"2016","journal-title":"J. Med. Entomol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1093\/jmedent\/43.3.600","article-title":"Ixodes Scapularis Ticks Collected by Passive Surveillance in Canada: Analysis of Geographic Distribution and Infection with Lyme Borreliosis Agent Borrelia Burgdorferi","volume":"43","author":"Ogden","year":"2006","journal-title":"J. Med. Entomol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Descamps, S. (2013). Winter Temperature Affects the Prevalence of Ticks in an Arctic Seabird. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065374"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1089\/vbz.2010.0009","article-title":"Worldwide Distribution and Diversity of Seabird Ticks: Implications for the Ecology and Epidemiology of Tick-Borne Pathogens","volume":"11","author":"Dietrich","year":"2011","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.3201\/eid1212.060448","article-title":"Borrelia Garinii in Seabird Ticks (Ixodes Uriae), Atlantic Coast, North America","volume":"12","author":"Smith","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01087-17","DOI":"10.1128\/AEM.01087-17","article-title":"Evidence for Borrelia Bavariensis Infections of Ixodes Uriae within Seabird Colonies of the North Atlantic Ocean","volume":"83","author":"Munro","year":"2017","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/362340a0","article-title":"A Lyme Borreliosis Cycle in Seabirds and Ixodes Uriae Ticks","volume":"362","author":"Jaenson","year":"1993","journal-title":"Nature"},{"key":"ref_26","unstructured":"U.S. Centers for Disease Control and Prevention (2019). Others What You Need To Know about Asian Longhorned Ticks-A New Tick in the United States, CDC."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nuttall, P. (2021). Climate, Ticks and Disease, CABI.","DOI":"10.1079\/9781789249637.0000"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.15585\/mmwr.mm6747a3","article-title":"Multistate Infestation with the Exotic Disease\u2013Vector Tick Haemaphysalis Longicornis\u2014United States, August 2017\u2013September 2018","volume":"67","author":"Beard","year":"2018","journal-title":"MMWR. Morbid. Mortal. Wkly Rep."},{"key":"ref_29","unstructured":"(2022, February 09). CDC Regions Where Ticks Live, Available online: https:\/\/www.cdc.gov\/ticks\/geographic_distribution.html."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101495","DOI":"10.1016\/j.ttbdis.2020.101495","article-title":"Establishing a Baseline for Tick Surveillance in Alaska: Tick Collection Records from 1909-2019","volume":"11","author":"Hahn","year":"2020","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/art.1780200102","article-title":"Lyme arthritis: An epidemic of oligoarticular arthritis in children and adults in three Connecticut communities","volume":"20","author":"Steere","year":"1977","journal-title":"Arthritis Rheum."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/21548331.1978.11707320","article-title":"Lyme Arthritis: A New Clinical Entity","volume":"13","author":"Steere","year":"1978","journal-title":"Hosp. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e02166-19","DOI":"10.1128\/mBio.02166-19","article-title":"Discovery of the Lyme Disease Agent","volume":"10","author":"Barbour","year":"2019","journal-title":"MBio"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"818","DOI":"10.4269\/ajtmh.1983.32.818","article-title":"Spirochetes in Ixodes Dammini and Mammals from Connecticut","volume":"32","author":"Anderson","year":"1983","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.6836274","article-title":"Natural Distribution of the Ixodes Dammini Spirochete","volume":"220","author":"Bosler","year":"1983","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1056\/NEJM198303313081302","article-title":"Spirochetes Isolated from the Blood of Two Patients with Lyme Disease","volume":"308","author":"Benach","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1056\/NEJM198303313081301","article-title":"The Spirochetal Etiology of Lyme Disease","volume":"308","author":"Steere","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1126\/science.7043737","article-title":"Lyme Disease\u2014A Tick-Borne Spirochetosis?","volume":"216","author":"Burgdorfer","year":"1982","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/jmedent\/30.1.54","article-title":"Conspecificity of the Ticks Ixodes Scapularis and I. Dammini (Acari: Ixodidae)","volume":"30","author":"Oliver","year":"1993","journal-title":"J. Med. Entomol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1128\/jcm.25.3.557-558.1987","article-title":"Duration of Tick Attachment and Borrelia Burgdorferi Transmission","volume":"25","author":"Piesman","year":"1987","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2307\/3283916","article-title":"Transmission of Borrelia Burgdorferi by Ixodes Pacificus Nymphs and Reservoir Competence of Deer Mice (Peromyscus Maniculatus) Infected by Tick-Bite","volume":"81","author":"Peavey","year":"1995","journal-title":"J. Parasitol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/jmedent\/31.3.417","article-title":"Vector Competence of Ixodes Pacificus and Dermacentor Occidentalis (Acari: Ixodidae) for Various Isolates of Lyme Disease Spirochetes","volume":"31","author":"Lane","year":"1994","journal-title":"J. Med. Entomol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1093\/jmedent\/25.5.336","article-title":"Ability of Ixodes Scapularis, Dermacentor Variabilis, and Amblyomma Americanum (Acari: Ixodidae) to Acquire, Maintain, and Transmit Lyme Disease Spirochetes (Borrelia Burgdorferi)","volume":"25","author":"Piesman","year":"1988","journal-title":"J. Med. Entomol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.pt.2017.12.006","article-title":"The Blacklegged Tick, Ixodes Scapularis: An Increasing Public Health Concern","volume":"34","author":"Eisen","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ttbdis.2011.11.004","article-title":"Synchronous Phenology of Juvenile Ixodes Scapularis, Vertebrate Host Relationships, and Associated Patterns of Borrelia Burgdorferi Ribotypes in the Midwestern United States","volume":"3","author":"Hamer","year":"2012","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Hunter, D.J., Torkelson, J.L., Bodnar, J., Mortazavi, B., Laurent, T., Deason, J., Thephavongsa, K., and Zhong, J. (2015). The Rickettsia Endosymbiont of Ixodes Pacificus Contains All the Genes of De Novo Folate Biosynthesis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144552"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.pt.2013.04.002","article-title":"New Insights into the Machinery of Blood Digestion by Ticks","volume":"29","author":"Sojka","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4269\/ajtmh.1996.54.84","article-title":"Reservoir Competence of Four Chaparral-Dwelling Rodents for Borrelia Burgdorferi in California","volume":"54","author":"Brown","year":"1996","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fimmu.2017.00116","article-title":"Borrelia Burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts","volume":"8","author":"Tracy","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.4269\/ajtmh.2009.09-0208","article-title":"Niche Partitioning of Borrelia Burgdorferi and Borrelia Miyamotoi in the Same Tick Vector and Mammalian Reservoir Species","volume":"81","author":"Barbour","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.pt.2015.03.010","article-title":"Tick Microbiome: The Force within","volume":"31","author":"Narasimhan","year":"2015","journal-title":"Trends Parasitol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Institute of Medicine (US) Committee on Lyme Disease, and Other Tick-Borne Diseases: The State of the Science (2011). An Overview of Tick-Borne Diseases, National Academies Press (US).","DOI":"10.69645\/ISPV3159"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"535","DOI":"10.4269\/ajtmh.2008.79.535","article-title":"Identifying the Reservoir Hosts of the Lyme Disease Spirochete Borrelia Burgdorferi in California: The Role of the Western Gray Squirrel (Sciurus Griseus)","volume":"79","author":"Salkeld","year":"2008","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104719","DOI":"10.1016\/j.meegid.2021.104719","article-title":"Bats Are Key Hosts in the Radiation of Mammal-Associated Bartonella Bacteria","volume":"89","author":"McKee","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.3201\/eid1812.111392","article-title":"Reservoir Competence of Wildlife Host Species for Babesia Microti","volume":"18","author":"Hersh","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1093\/jme\/tjv092","article-title":"American Black Bears as Hosts of Blacklegged Ticks (Acari: Ixodidae) in the Northeastern United States","volume":"52","author":"Zolnik","year":"2015","journal-title":"J. Med. Entomol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.ttbdis.2018.04.006","article-title":"The Role of Ixodes Scapularis, Borrelia Burgdorferi and Wildlife Hosts in Lyme Disease Prevalence: A Quantitative Review","volume":"9","author":"Halsey","year":"2018","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101761","DOI":"10.1016\/j.ttbdis.2021.101761","article-title":"Lake Michigan Insights from Island Studies: The Roles of Chipmunks and Coyotes in Maintaining Ixodes Scapularis and Borrelia Burgdorferi in the Absence of White-Tailed Deer","volume":"12","author":"Sidge","year":"2021","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/jmedent\/26.4.272","article-title":"Lyme Disease in California: Interrelationship of Ixodes Pacificus (Acari: Ixodidae), the Western Fence Lizard (Sceloporus Occidentalis), and Borrelia Burgdorferi","volume":"26","author":"Lane","year":"1989","journal-title":"J. Med. Entomol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1023\/B:APPA.0000032954.71165.9e","article-title":"Habitat-Related Variation in Infestation of Lizards and Rodents with Ixodes Ticks in Dense Woodlands in Mendocino County, California","volume":"33","author":"Eisen","year":"2004","journal-title":"Exp. Appl. Acarol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1023\/A:1020911306291","article-title":"Relative Importance of Lizards and Mammals as Hosts for Ixodid Ticks in Northern California","volume":"26","author":"Casher","year":"2002","journal-title":"Exp. Appl. Acarol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1086\/319347","article-title":"Ticks and Tickborne Bacterial Diseases in Humans: An Emerging Infectious Threat","volume":"32","author":"Parola","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijppaw.2012.11.003","article-title":"Natural History of Zoonotic Babesia: Role of Wildlife Reservoirs","volume":"2","author":"Yabsley","year":"2013","journal-title":"Int. J. Parasitol. Parasites Wildl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.vetpar.2009.09.013","article-title":"The Natural History of Anaplasma Phagocytophilum","volume":"167","author":"Woldehiwet","year":"2010","journal-title":"Vet. Parasitol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1099\/00207713-45-4-804","article-title":"Genetic and Phenotypic Analysis of Borrelia Miyamotoi Sp. Nov., Isolated from the Ixodid Tick Ixodes Persulcatus, the Vector for Lyme Disease in Japan","volume":"45","author":"Fukunaga","year":"1995","journal-title":"Int. J. Syst. Bacteriol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kingry, L.C., Batra, D., Replogle, A., Rowe, L.A., Pritt, B.S., and Petersen, J.M. (2016). Whole Genome Sequence and Comparative Genomics of the Novel Lyme Borreliosis Causing Pathogen, Borrelia Mayonii. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168994"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1128\/CMR.16.1.37-64.2003","article-title":"Ehrlichia Chaffeensis: A Prototypical Emerging Pathogen","volume":"16","author":"Paddock","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa1010493","article-title":"Emergence of a New Pathogenic Ehrlichia Species, Wisconsin and Minnesota, 2009","volume":"365","author":"Pritt","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_69","first-page":"61","article-title":"Chapin Bacterium Tularense, the Cause of a Plague-like Disease of Rodents","volume":"10","author":"McCoy","year":"1912","journal-title":"J. Infect. Dis. (Public Health Bull.)"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1086\/381894","article-title":"Rickettsia Parkeri: A Newly Recognized Cause of Spotted Fever Rickettsiosis in the United States","volume":"38","author":"Paddock","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3201\/eid2105.150150","article-title":"Novel Thogotovirus Associated with Febrile Illness and Death, United States, 2014","volume":"21","author":"Kosoy","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4049\/jimmunol.64.4.257","article-title":"Colorado Tick Fever: Isolation of the Virus from Dermacentor Andersoni in Nature and a Laboratory Study of the Transmission of the Virus in the Tick","volume":"64","author":"Florio","year":"1950","journal-title":"J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1056\/NEJMoa1203378","article-title":"A New Phlebovirus Associated with Severe Febrile Illness in Missouri","volume":"367","author":"McMullan","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_74","first-page":"708","article-title":"Powassan Virus: Isolation of Virus from a Fatal Case of Encephalitis","volume":"80","author":"McLEAN","year":"1959","journal-title":"Can. Med. Assoc. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"180017","DOI":"10.2807\/1560-7917.ES.2019.24.18.1800170","article-title":"A New Borrelia on the Block: Borrelia Miyamotoi\u2014A Human Health Risk?","volume":"24","author":"Cutler","year":"2019","journal-title":"Euro. Surveill."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1093\/jme\/tjx062","article-title":"Isolation of the Lyme Disease Spirochete Borrelia Mayonii From Naturally Infected Rodents in Minnesota","volume":"54","author":"Johnson","year":"2017","journal-title":"J. Med. Entomol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/jme\/tjab215","article-title":"The Original Scientific Description of the Lone Star Tick (Amblyomma Americanum, Acari: Ixodidae) and Implications for the Species\u2019 Past and Future Geographic Distributions","volume":"59","author":"Rochlin","year":"2022","journal-title":"J. Med. Entomol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/jme\/tjx250","article-title":"Amblyomma Americanum (Acari: Ixodidae) Ticks Are Not Vectors of the Lyme Disease Agent, Borrelia Burgdorferi (Spirocheatales: Spirochaetaceae): A Review of the Evidence","volume":"55","author":"Stromdahl","year":"2018","journal-title":"J. Med. Entomol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"925","DOI":"10.4269\/ajtmh.1985.34.925","article-title":"The Western Black-Legged Tick, Ixodes Pacificus: A Vector of Borrelia Burgdorferi","volume":"34","author":"Burgdorfer","year":"1985","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1603\/0022-2585-38.5.684","article-title":"Life Cycle of Ixodes Pacificus (Acari: Ixodidae): Timing of Developmental Processes under Field and Laboratory Conditions","volume":"38","author":"Padgett","year":"2001","journal-title":"J. Med. Entomol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1128\/JCM.39.4.1221-1226.2001","article-title":"Molecular Evidence of Bartonella Spp. in Questing Adult Ixodes Pacificus Ticks in California","volume":"39","author":"Chang","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.ttbdis.2014.02.002","article-title":"Surveillance for Ixodes Pacificus and the Tick-Borne Pathogens Anaplasma Phagocytophilum and Borrelia Burgdorferi in Birds from California\u2019s Inner Coast Range","volume":"5","author":"Dingler","year":"2014","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6578","DOI":"10.1111\/mec.14391","article-title":"Vertical vs. Horizontal Transmission of the Microbiome in a Key Disease Vector, Ixodes Pacificus","volume":"26","author":"Kwan","year":"2017","journal-title":"Mol. Ecol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/jmedent\/25.5.391","article-title":"Questing Behavior of Ixodes Pacificus (Acari: Ixodidae) in Relation to Meteorological and Seasonal Factors","volume":"25","author":"Loye","year":"1988","journal-title":"J. Med. Entomol."},{"key":"ref_85","first-page":"8","article-title":"Ome SweetOmics\u2014A Genealogical Treasury of Words","volume":"15","author":"Lederberg","year":"2001","journal-title":"Scientist"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.mib.2018.01.013","article-title":"The Soil Microbiome\u2014From Metagenomics to Metaphenomics","volume":"43","author":"Jansson","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1261359","DOI":"10.1126\/science.1261359","article-title":"Ocean Plankton. Structure and Function of the Global Ocean Microbiome","volume":"348","author":"Sunagawa","year":"2015","journal-title":"Science"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nature06244","article-title":"The Human Microbiome Project","volume":"449","author":"Turnbaugh","year":"2007","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/gb-2008-9-6-225","article-title":"What Makes Pathogens Pathogenic","volume":"9","author":"Ehrlich","year":"2008","journal-title":"Genome Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3389\/fcimb.2017.00236","article-title":"The Tick Microbiome: Why Non-Pathogenic Microorganisms Matter in Tick Biology and Pathogen Transmission","volume":"7","author":"Bonnet","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Estrada-Pe\u00f1a, A., Cabezas-Cruz, A., and Obreg\u00f3n, D. (2020). Behind Taxonomic Variability: The Functional Redundancy in the Tick Microbiome. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111829"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3389\/fvets.2017.00179","article-title":"Microbial Communities in North American Ixodid Ticks of Veterinary and Medical Importance","volume":"4","author":"Park","year":"2017","journal-title":"Front. Vet. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhong, J., Jasinskas, A., and Barbour, A.G. (2007). Antibiotic Treatment of the Tick Vector Amblyomma Americanum Reduced Reproductive Fitness. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000405"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"854803","DOI":"10.3389\/fmicb.2022.854803","article-title":"The Symbiotic Continuum Within Ticks: Opportunities for Disease Control","volume":"13","author":"Hussain","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.chom.2021.08.011","article-title":"Symbiont-Regulated Serotonin Biosynthesis Modulates Tick Feeding Activity","volume":"29","author":"Zhong","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1038\/s41396-018-0161-6","article-title":"Ixodes Scapularis Does Not Harbor a Stable Midgut Microbiome","volume":"12","author":"Ross","year":"2018","journal-title":"ISME J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ttbdis.2018.01.007","article-title":"Transient Influence of Blood Meal and Natural Environment on Blacklegged Tick Bacterial Communities","volume":"9","author":"Zolnik","year":"2018","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Thapa, S., Zhang, Y., and Allen, M.S. (2019). Bacterial Microbiomes of Ixodes Scapularis Ticks Collected from Massachusetts and Texas, USA. BMC Microbiol., 19.","DOI":"10.1186\/s12866-019-1514-7"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fcimb.2019.00298","article-title":"Sex-Specific Linkages Between Taxonomic and Functional Profiles of Tick Gut Microbiomes","volume":"9","author":"Bard","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s13199-019-00642-2","article-title":"Diversity and Structure of the Bacterial Microbiome of the American Dog Tick, Dermacentor Variabilis, Is Dominated by the Endosymbiont Francisella","volume":"79","author":"Travanty","year":"2019","journal-title":"Symbiosis"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Brinkerhoff, R.J., Clark, C., Ocasio, K., Gauthier, D.T., and Hynes, W.L. (2020). Factors Affecting the Microbiome of Ixodes Scapularis and Amblyomma Americanum. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232398"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Chicana, B., Couper, L.I., Kwan, J.Y., Tahiraj, E., and Swei, A. (2019). Comparative Microbiome Profiles of Sympatric Tick Species from the Far-Western United States. Insects, 10.","DOI":"10.3390\/insects10100353"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.crpvbd.2021.100036","article-title":"Current Debates and Advances in Tick Microbiome Research","volume":"1","author":"Obregon","year":"2021","journal-title":"Curr Res Parasitol Vector Borne Dis"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Williams-Newkirk, A.J., Rowe, L.A., Mixson-Hayden, T.R., and Dasch, G.A. (2014). Characterization of the Bacterial Communities of Life Stages of Free Living Lone Star Ticks (Amblyomma Americanum). PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102130"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"101321","DOI":"10.1016\/j.ttbdis.2019.101321","article-title":"Microbiota Assessment across Different Developmental Stages of Dermacentor Silvarum (Acari: Ixodidae) Revealed Stage-Specific Signatures","volume":"11","author":"Zhang","year":"2020","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Eshoo, M.W., Carolan, H.E., Massire, C., Chou, D.M., Crowder, C.D., Rounds, M.A., Phillipson, C.A., Schutzer, S.E., and Ecker, D.J. (2015). Survey of Ixodes Pacificus Ticks in California Reveals a Diversity of Microorganisms and a Novel and Widespread Anaplasmataceae Species. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135828"},{"key":"ref_107","first-page":"404","article-title":"Verhandlungen Der Dermatologischen Gesellschaft Zu Stockholm","volume":"101","author":"Afzelius","year":"1910","journal-title":"Arch. Dermatol. Syph."},{"key":"ref_108","first-page":"227","article-title":"Erythema Chronicum Migrans Afzelius with Meningitis","volume":"31","author":"Hellerstrom","year":"1951","journal-title":"Acta Derm. Venereol."},{"key":"ref_109","first-page":"7","article-title":"Paralysie Par Les Tiques","volume":"71","author":"Garin","year":"1922","journal-title":"J. Med. Lyon"},{"key":"ref_110","unstructured":"Benach, J., and Garcia Monco, J. (2010). The Woldwide Saga of Lyme Borreliosis. Borrelia. Molecular Biology, Host Interaction and Pathogenesis, Caister Academic Press."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"685","DOI":"10.7326\/0003-4819-86-6-685","article-title":"Erythema Chronicum Migrans and Lyme Arthritis. The Enlarging Clinical Spectrum","volume":"86","author":"Steere","year":"1977","journal-title":"Ann. Intern. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/00005792-197907000-00001","article-title":"Neurologic Abnormalities of Lyme Disease","volume":"58","author":"Reik","year":"1979","journal-title":"Medicine"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1038\/s41559-017-0282-8","article-title":"Genomic Insights into the Ancient Spread of Lyme Disease across North America","volume":"1","author":"Walter","year":"2017","journal-title":"Nat Ecol Evol"},{"key":"ref_114","unstructured":"Barrett, A.D.T., and Stanberry, L.R. (2009). Chapter 52\u2014Lyme Disease. Vaccines for Biodefense and Emerging and Neglected Diseases, Academic Press."},{"key":"ref_115","unstructured":"(2019, April 25). Data and Surveillance Lyme Disease|CDC, Available online: https:\/\/www.cdc.gov\/lyme\/datasurveillance\/index.html."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.idc.2008.03.006","article-title":"Tick-Borne Relapsing Fever","volume":"22","author":"Dworkin","year":"2008","journal-title":"Infect. Dis. Clin. North Am."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S1473-3099(15)00464-8","article-title":"Identification of a Novel Pathogenic Borrelia Species Causing Lyme Borreliosis with Unusually High Spirochaetaemia: A Descriptive Study","volume":"16","author":"Pritt","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Crowder, C.D., Matthews, H.E., Schutzer, S., Rounds, M.A., Luft, B.J., Nolte, O., Campbell, S.R., Phillipson, C.A., Li, F., and Sampath, R. (2010). Genotypic Variation and Mixtures of Lyme Borrelia in Ixodes Ticks from North America and Europe. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010650"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.meegid.2011.07.022","article-title":"Population Genetics, Taxonomy, Phylogeny and Evolution of Borrelia Burgdorferi Sensu Lato","volume":"11","author":"Margos","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1099\/00207713-46-4-859","article-title":"Phylogenesis of Relapsing Fever Borrelia spp.","volume":"46","author":"Ras","year":"1996","journal-title":"Int. J. Syst. Bacteriol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s10482-014-0164-x","article-title":"A Phylogenomic and Molecular Marker Based Proposal for the Division of the Genus Borrelia into Two Genera: The Emended Genus Borrelia Containing Only the Members of the Relapsing Fever Borrelia, and the Genus Borreliella Gen. Nov. Containing the Members of the Lyme Disease Borrelia (Borrelia Burgdorferi Sensu Lato Complex)","volume":"105","author":"Adeolu","year":"2014","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2165\/0128071-200809060-00002","article-title":"Skin Manifestations of Lyme Borreliosis","volume":"9","author":"Glatz","year":"2008","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.4081\/idr.2014.5496","article-title":"A Case of Chronic Progressive Lyme Encephalitis as a Manifestation of Late Lyme Neuroborreliosis","volume":"6","author":"Verma","year":"2014","journal-title":"Infect. Dis. Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"629","DOI":"10.12740\/PP\/97336","article-title":"Psychosis in Borrelia Burgdorferi Infection\u2014Part I: Epidemiology, Pathogenesis, Diagnosis and Treatment of Neuroborreliosis","volume":"53","author":"Nasierowski","year":"2019","journal-title":"Psychiatr. Pol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/00006454-200204000-00021","article-title":"Cerebellar Ataxia as the Presenting Manifestation of Lyme Disease","volume":"21","author":"Crawford","year":"2002","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_126","first-page":"751","article-title":"Lyme Neuroborreliosis","volume":"115","author":"Rauer","year":"2018","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10096-018-3417-1","article-title":"Clinical Spectrum of Lyme Disease","volume":"38","author":"Welsh","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.5858\/2003-127-1204-LPANCS","article-title":"Lyme-Associated Parkinsonism: A Neuropathologic Case Study and Review of the Literature","volume":"127","author":"Cassarino","year":"2003","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0140-6736(11)60103-7","article-title":"Lyme Borreliosis","volume":"379","author":"Stanek","year":"2012","journal-title":"Lancet"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.3233\/JAD-130446","article-title":"Lyme Neuroborreliosis and Dementia","volume":"41","author":"Blanc","year":"2014","journal-title":"J. Alzheimers. Dis."},{"key":"ref_131","first-page":"453","article-title":"The Clinical Spectrum and Treatment of Lyme Disease","volume":"57","author":"Steere","year":"1984","journal-title":"Yale J. Biol. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1093\/aje\/152.8.756","article-title":"Racial Differences in Reported Lyme Disease Incidence","volume":"152","author":"Fix","year":"2000","journal-title":"Am. J. Epidemiol."},{"key":"ref_133","first-page":"473","article-title":"Lyme Disease Pathogenesis","volume":"42","author":"Coburn","year":"2020","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1001\/jamadermatol.2018.3186","article-title":"Efficacy and Safety of Antibiotic Therapy in Early Cutaneous Lyme Borreliosis: A Network Meta-Analysis","volume":"154","author":"Torbahn","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.idc.2007.12.013","article-title":"Biology of Infection with Borrelia Burgdorferi","volume":"22","author":"Tilly","year":"2008","journal-title":"Infect. Dis. Clin. North Am."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/s41564-021-01003-w","article-title":"The Unusual Cell Wall of the Lyme Disease Spirochaete Borrelia Burgdorferi Is Shaped by a Tick Sugar","volume":"6","author":"DeHart","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"10899","DOI":"10.1073\/pnas.200221797","article-title":"Borrelia Burgdorferi Periplasmic Flagella Have Both Skeletal and Motility Functions","volume":"97","author":"Motaleb","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Sapi, E., Bastian, S.L., Mpoy, C.M., Scott, S., Rattelle, A., Pabbati, N., Poruri, A., Burugu, D., Theophilus, P.A.S., and Pham, T.V. (2012). Characterization of Biofilm Formation by Borrelia Burgdorferi in Vitro. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048277"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1556\/1886.2015.00049","article-title":"Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas","volume":"6","author":"Sapi","year":"2016","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"fnv120","DOI":"10.1093\/femsle\/fnv120","article-title":"Biofilm Formation by Borrelia Burgdorferi Sensu Lato","volume":"362","author":"Timmaraju","year":"2015","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1099\/mic.0.000380","article-title":"Influence of Tick and Mammalian Physiological Temperatures on Borrelia Burgdorferi Biofilms","volume":"162","author":"Shaikh","year":"2016","journal-title":"Microbiology"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1186\/s13071-019-3495-7","article-title":"Metamorphoses of Lyme Disease Spirochetes: Phenomenon of Borrelia Persisters","volume":"12","author":"Rudenko","year":"2019","journal-title":"Parasit. Vectors"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cell.2004.10.027","article-title":"TROSPA, an Ixodes Scapularis Receptor for Borrelia Burgdorferi","volume":"119","author":"Pal","year":"2004","journal-title":"Cell"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41579-020-0400-5","article-title":"Interactions between Borrelia Burgdorferi and Ticks","volume":"18","author":"Kurokawa","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.pt.2007.07.001","article-title":"Tick\u2013host\u2013pathogen Interactions in Lyme Borreliosis","volume":"23","author":"Hovius","year":"2007","journal-title":"Trends Parasitol."},{"key":"ref_146","unstructured":"(2022, March 17). CDC Transmission, Available online: https:\/\/www.cdc.gov\/lyme\/transmission\/index.html."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.ttbdis.2018.01.002","article-title":"Pathogen Transmission in Relation to Duration of Attachment by Ixodes Scapularis Ticks","volume":"9","author":"Eisen","year":"2018","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_148","first-page":"1","article-title":"Lyme Borreliosis: A Review of Data on Transmission Time after Tick Attachment","volume":"8","author":"Cook","year":"2015","journal-title":"Int. J. Gen. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fimmu.2017.00114","article-title":"Borrelia Burgdorferi Keeps Moving and Carries on: A Review of Borrelial Dissemination and Invasion","volume":"8","author":"Hyde","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_150","first-page":"233","article-title":"Innate Immunity Networks during Infection with Borrelia Burgdorferi","volume":"42","author":"Oosting","year":"2016","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_151","first-page":"145","article-title":"Immune response to Borrelia: Lessons from Lyme disease spirochetes","volume":"42","author":"Bockenstedt","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.4049\/jimmunol.1103735","article-title":"Delays and Diversions Mark the Development of B Cell Responses to Borrelia Burgdorferi Infection","volume":"188","author":"Elsner","year":"2012","journal-title":"J. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1128\/IAI.02471-14","article-title":"CD4+ T Cells Promote Antibody Production but Not Sustained Affinity Maturation during Borrelia Burgdorferi Infection","volume":"83","author":"Elsner","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.3389\/fimmu.2020.01560","article-title":"Immune Evasion Strategies of Relapsing Fever Spirochetes","volume":"11","author":"Kraiczy","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e00481-13","DOI":"10.1128\/mBio.00481-13","article-title":"CspA from Borrelia Burgdorferi Inhibits the Terminal Complement Pathway","volume":"4","author":"Siegel","year":"2013","journal-title":"MBio"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Hart, T., Nguyen, N.T.T., Nowak, N.A., Zhang, F., Linhardt, R.J., Diuk-Wasser, M., Ram, S., Kraiczy, P., and Lin, Y.-P. (2018). Polymorphic Factor H-Binding Activity of CspA Protects Lyme Borreliae from the Host Complement in Feeding Ticks to Facilitate Tick-to-Host Transmission. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007106"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2020.00001","article-title":"New Insights Into CRASP-Mediated Complement Evasion in the Lyme Disease Enzootic Cycle","volume":"10","author":"Lin","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Garcia, B.L., Zhi, H., Wager, B., H\u00f6\u00f6k, M., and Skare, J.T. (2016). Borrelia Burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005404"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3389\/fimmu.2016.00385","article-title":"Hide and Seek: How Lyme Disease Spirochetes Overcome Complement Attack","volume":"7","author":"Kraiczy","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Locke, J.W. (2019). Complement Evasion in Borrelia Spirochetes: Mechanisms and Opportunities for Intervention. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020080"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"25229","DOI":"10.1074\/jbc.M112.413872","article-title":"BBA70 of Borrelia Burgdorferi Is a Novel Plasminogen-Binding Protein","volume":"288","author":"Koenigs","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fcimb.2018.00098","article-title":"Relapsing Fevers: Neglected Tick-Borne Diseases","volume":"8","author":"Boyer","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1111\/j.1365-2672.2009.04598.x","article-title":"Relapsing Fever\u2014A Forgotten Disease Revealed","volume":"108","author":"Cutler","year":"2010","journal-title":"J. Appl. Microbiol."},{"key":"ref_164","first-page":"58","article-title":"Tickborne Relapsing Fever\u2014United States, 1990\u20132011","volume":"64","author":"Forrester","year":"2015","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_165","unstructured":"(2022, February 10). CDC Symptoms, Available online: https:\/\/www.cdc.gov\/relapsing-fever\/symptoms\/index.html."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Lopez, J., Hovius, J.W., and Bergstr\u00f6m, S. (2021). Pathogenesis of Relapsing Fever. Lyme Disease and Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions and Disease Pathogenesis 2021, Caister Academic Press.","DOI":"10.21775\/9781913652616.14"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Adrion, E.R., Aucott, J., Lemke, K.W., and Weiner, J.P. (2015). Health Care Costs, Utilization and Patterns of Care Following Lyme Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116767"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1542\/peds.2007-0484","article-title":"Burden and Economic Cost of Group A Streptococcal Pharyngitis","volume":"121","author":"Pfoh","year":"2008","journal-title":"Pediatrics"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"574806","DOI":"10.3389\/fcimb.2020.574806","article-title":"Laboratory Diagnostic Tools for Syphilis: Current Status and Future Prospects","volume":"10","author":"Luo","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1093\/cid\/ciy558","article-title":"Performance of Treponemal Tests for the Diagnosis of Syphilis","volume":"68","author":"Park","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_171","first-page":"666","article-title":"Diagnosing Streptococcal Sore Throat in Adults: Randomized Controlled Trial of in-Office Aids","volume":"53","author":"Worrall","year":"2007","journal-title":"Can. Fam. Phys."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jmoldx.2020.05.003","article-title":"Diagnostic Accuracy of Presurgical Staphylococcus Aureus PCR Assay Compared with Culture and Post-PCR Implementation Surgical Site Infection Rates","volume":"22","author":"Tansarli","year":"2020","journal-title":"J. Mol. Diagn."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1128\/CMR.10.1.185","article-title":"PCR in Laboratory Diagnosis of Human Borrelia Burgdorferi Infections","volume":"10","author":"Schmidt","year":"1997","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Aucott, J., Morrison, C., Munoz, B., Rowe, P.C., Schwarzwalder, A., and West, S.K. (2009). Diagnostic Challenges of Early Lyme Disease: Lessons from a Community Case Series. BMC Infect. Dis., 9.","DOI":"10.1186\/1471-2334-9-79"},{"key":"ref_175","first-page":"50","article-title":"It\u2019s about Lyme: Why Congress Must Enact Medical Insurance Coverage Laws for Lyme Disease Patients Now","volume":"45","author":"Barrett","year":"2022","journal-title":"Seattle U. L. Rev. SUpra"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"St Pierre, S.E., Gould, O.N., and Lloyd, V. (2020). Knowledge and Knowledge Needs about Lyme Disease among Occupational and Recreational Users of the Outdoors. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17010355"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.3201\/eid2207.151694","article-title":"Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States","volume":"22","author":"Moore","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Waddell, L.A., Greig, J., Mascarenhas, M., Harding, S., Lindsay, R., and Ogden, N. (2016). The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168613"},{"key":"ref_179","unstructured":"Radolf, J.D., and Scott Samuels, D. (2010). Borrelia: Molecular Biology, Host Interaction and Pathogenesis, Horizon Scientific Press."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.idc.2015.02.005","article-title":"Laboratory Diagnosis of Lyme Disease: Advances and Challenges","volume":"29","author":"Marques","year":"2015","journal-title":"Infect. Dis. Clin. North Am."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"582","DOI":"10.3947\/ic.2021.0008","article-title":"Ceftriaxone and Doxycycline Induced Seroconversion in Previously Seronegative Patient with Clinically Suspected Disseminated Lyme Disease: Case Report","volume":"53","author":"Zagorac","year":"2021","journal-title":"Infect Chemother."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1574-695X.1997.tb01078.x","article-title":"Advances and Pitfalls in the Diagnosis of Lyme Disease","volume":"19","author":"Coyle","year":"1997","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Anderson, C., and Brissette, C.A. (2021). The Brilliance of Borrelia: Mechanisms of Host Immune Evasion by Lyme Disease-Causing Spirochetes. Pathogens, 10.","DOI":"10.3390\/pathogens10030281"},{"key":"ref_184","unstructured":"Wang, G., Aguero-Rosenfeld, M.E., and Wormser, G.P. (2010). Detection of Borrelia Burgdorferi, Caister Academic Press."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF03262098","article-title":"Molecular Diagnosis of Lyme Disease: Review and Meta-Analysis","volume":"6","author":"Dumler","year":"2001","journal-title":"Mol. Diagn."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/j.1469-0691.2004.00895.x","article-title":"Lyme Borreliosis: From Infection to Autoimmunity","volume":"10","author":"Singh","year":"2004","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_187","unstructured":"Norris, S.J., Coburn, J., Leong, J.M., Hu, L.T., and Hook, M. (2010). Pathobiology of Lyme Disease Borrelia. Borrelia: Molecular Biology, Host Interaction And Pathogenesis, Horizon Scientific Press."},{"key":"ref_188","unstructured":"Barbour, A.G., and Guo, B.P. (2010). Pathogenesis of Relapsing Fever. Borrelia Mol. Biol. Host Interact. Pathogenesis, 333\u2013357."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00508-005-0361-8","article-title":"A Comparison of Two Treatment Regimens of Ceftriaxone in Late Lyme Disease","volume":"117","author":"Dattwyler","year":"2005","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"819541","DOI":"10.3389\/fpubh.2021.819541","article-title":"What We Know and Don\u2019t Know About Lyme Disease","volume":"9","author":"Donta","year":"2021","journal-title":"Front Public Health"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1038\/s41598-018-21349-2","article-title":"A Multiplex Serologic Platform for Diagnosis of Tick-Borne Diseases","volume":"8","author":"Tokarz","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fcimb.2014.00074","article-title":"Lyme and Associated Tick-Borne Diseases: Global Challenges in the Context of a Public Health Threat","volume":"4","author":"Perronne","year":"2014","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s15010-010-0062-8","article-title":"Isolation of Borrelia Burgdorferi Sensu Lato from Blood of Adult Patients with Borrelial Lymphocytoma, Lyme Neuroborreliosis, Lyme Arthritis and Acrodermatitis Chronica Atrophicans","volume":"39","author":"Maraspin","year":"2011","journal-title":"Infection"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/infdis\/158.4.905","article-title":"Cultivation of Borrelia Burgdorferi from Joint Fluid Three Months after Treatment of Facial Palsy due to Lyme Borreliosis","volume":"158","author":"Schmidli","year":"1988","journal-title":"J. Infect. Dis."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1056\/NEJM199001253220407","article-title":"Isolation of Borrelia Burgdorferi from the Myocardium of a Patient with Long-Standing Cardiomyopathy","volume":"322","author":"Stanek","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_196","first-page":"155","article-title":"First Isolation of Borrelia Burgdorferi from an Iris Biopsy","volume":"13","author":"Pfister","year":"1993","journal-title":"J. Clin. Neuroophthalmol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"e182","DOI":"10.1016\/j.ijid.2010.11.002","article-title":"First Isolation and Molecular Identification of Borrelia Burgdorferi Sensu Stricto and Borrelia Afzelii from Skin Biopsies of Patients in Taiwan","volume":"15","author":"Chao","year":"2011","journal-title":"Int. J. Infect. Dis."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.diagmicrobio.2012.03.026","article-title":"Comparison of Five Diagnostic Modalities for Direct Detection of Borrelia Burgdorferi in Patients with Early Lyme Disease","volume":"73","author":"Liveris","year":"2012","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1128\/JCM.40.4.1249-1253.2002","article-title":"Quantitative Detection of Borrelia Burgdorferi in 2-Millimeter Skin Samples of Erythema Migrans Lesions: Correlation of Results with Clinical and Laboratory Findings","volume":"40","author":"Liveris","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Eshoo, M.W., Crowder, C.C., Rebman, A.W., Rounds, M.A., Matthews, H.E., Picuri, J.M., Soloski, M.J., Ecker, D.J., Schutzer, S.E., and Aucott, J.N. (2012). Direct Molecular Detection and Genotyping of Borrelia Burgdorferi from Whole Blood of Patients with Early Lyme Disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036825"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"e00018-19","DOI":"10.1128\/CMR.00018-19","article-title":"Laboratory Diagnosis of Lyme Borreliosis","volume":"34","author":"Branda","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Lambert, J.S., Cook, M.J., Healy, J.E., Murtagh, R., Avramovic, G., and Lee, S.H. (2019). Metagenomic 16S rRNA Gene Sequencing Survey of Borrelia Species in Irish Samples of Ixodes Ricinus Ticks. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0209881"},{"key":"ref_203","first-page":"405","article-title":"PathoDNA, an Advanced Diagnostic for Lyme Disease & Co-Infections Utilizing next Generation DNA Sequencing with Greater Sensitivity and Selectivity than ELISA\/western Blot","volume":"11","author":"Schettig","year":"2021","journal-title":"Adv. Infect. Dis."},{"key":"ref_204","first-page":"910","article-title":"Critical Evaluation of Urine-Based PCR Assay for Diagnosis of Lyme Borreliosis","volume":"12","author":"Rauter","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"e00237-19","DOI":"10.1128\/AAC.00237-19","article-title":"Molecular Testing of Serial Blood Specimens from Patients with Early Lyme Disease during Treatment Reveals Changing Coinfection with Mixtures of Borrelia Burgdorferi Genotypes","volume":"63","author":"Mosel","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1586\/14737159.2013.850418","article-title":"Achieving Molecular Diagnostics for Lyme Disease","volume":"13","author":"Eshoo","year":"2013","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"e2355","DOI":"10.1093\/cid\/ciaa858","article-title":"Detection of Borrelia Burgdorferi Cell-Free DNA in Human Plasma Samples for Improved Diagnosis of Early Lyme Borreliosis","volume":"73","author":"Branda","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Lee, S.H., Healy, J.E., and Lambert, J.S. (2019). Single Core Genome Sequencing for Detection of Both Borrelia Burgdorferi Sensu Lato and Relapsing Fever Borrelia Species. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16101779"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Veas, F. (2011). Apolipoprotein H, an acute phase protein, a performing tool for ultra-sensitive detection and isolation of microorganisms from different origins. Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases, InTechOpen.","DOI":"10.5772\/1045"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mehy.2018.04.012","article-title":"Blood Cell Disruption to Significantly Improve the Borrelia PCR Detection Sensitivity in Borreliosis in Humans","volume":"116","author":"Lacout","year":"2018","journal-title":"Med. Hypotheses"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1743-422X-8-63","article-title":"Highly Sensitive Detection of the Group A Rotavirus Using Apolipoprotein H-Coated ELISA Plates Compared to Quantitative Real-Time PCR","volume":"8","author":"Adlhoch","year":"2011","journal-title":"Virol. J."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1053\/jhep.2001.20531","article-title":"Hepatitis B Virus Dane Particles Bind to Human Plasma Apolipoprotein H","volume":"33","author":"Stefas","year":"2001","journal-title":"Hepatology"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1089\/aid.1997.13.97","article-title":"Human Plasmatic Apolipoprotein H Binds Human Immunodeficiency Virus Type 1 and Type 2 Proteins","volume":"13","author":"Stefas","year":"1997","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Greissl, J., Pesesky, M., Dalai, S.C., Rebman, A.W., Soloski, M.J., Horn, E.J., Dines, J.N., Gittelman, R.M., Snyder, T.M., and Emerson, R.O. (2021). Immunosequencing of the T-Cell Receptor Repertoire Reveals Signatures Specific for Diagnosis and Characterization of Early Lyme Disease. bioRxiv.","DOI":"10.1101\/2021.07.30.21261353"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1093\/ofid\/ofy209.145","article-title":"1760. Interferon Gamma Release Assay for Diagnosis of Lyme Disease","volume":"5","author":"Hefter","year":"2018","journal-title":"Open Forum Infect Dis"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"651217","DOI":"10.3389\/fmicb.2021.651217","article-title":"Targeting Multicopy Prophage Genes for the Increased Detection of Borrelia Burgdorferi Sensu Lato (s.l.), the Causative Agents of Lyme Disease, in Blood","volume":"12","author":"Shan","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1021\/acs.jproteome.9b00569","article-title":"Measurement of Organ-Specific and Acute-Phase Blood Protein Levels in Early Lyme Disease","volume":"19","author":"Zhou","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1093\/cid\/cit939","article-title":"Xenodiagnosis to Detect Borrelia Burgdorferi Infection: A First-in-Human Study","volume":"58","author":"Marques","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.ttbdis.2019.06.002","article-title":"Borrelia Burgdorferi Chemotaxis toward Tick Protein Salp12 Contributes to Acquisition","volume":"10","author":"Murfin","year":"2019","journal-title":"Ticks Tick-Borne Dis."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"616","DOI":"10.4269\/ajtmh.2002.66.616","article-title":"Chemotactic Migration of the Lyme Disease Spirochete (Borrelia Burgdorferi) to Salivary Gland Extracts of Vector Ticks","volume":"66","author":"Shih","year":"2002","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Embers, M.E., Barthold, S.W., Borda, J.T., Bowers, L., Doyle, L., Hodzic, E., Jacobs, M.B., Hasenkampf, N.R., Martin, D.S., and Narasimhan, S. (2012). Persistence of Borrelia Burgdorferi in Rhesus Macaques Following Antibiotic Treatment of Disseminated Infection. PLoS ONE, 7.","DOI":"10.1371\/annotation\/4cafed66-fb84-4589-a001-131d9c50aea6"},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Embers, M.E., Hasenkampf, N.R., Jacobs, M.B., Tardo, A.C., Doyle-Meyers, L.A., Philipp, M.T., and Hodzic, E. (2017). Variable Manifestations, Diverse Seroreactivity and Post-Treatment Persistence in Non-Human Primates Exposed to Borrelia Burgdorferi by Tick Feeding. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189071"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1086\/345284","article-title":"Detection of Attenuated, Noninfectious Spirochetes inBorrelia burgdorferi\u2013Infected Mice after Antibiotic Treatment","volume":"186","author":"Bockenstedt","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1093\/cid\/civ185","article-title":"Development of a Metabolic Biosignature for Detection of Early Lyme Disease","volume":"60","author":"Molins","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1021\/acs.jproteome.9b00470","article-title":"Host Metabolic Response in Early Lyme Disease","volume":"19","author":"Fitzgerald","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"949118","DOI":"10.3389\/fimmu.2022.949118","article-title":"Acute lyme disease IgG N-linked glycans contrast the canonical inflammatory signature","volume":"13","author":"Grauzam","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/37551","article-title":"Genomic Sequence of a Lyme Disease Spirochaete, Borrelia Burgdorferi","volume":"390","author":"Fraser","year":"1997","journal-title":"Nature"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1046\/j.1365-2958.1999.01368.x","article-title":"Physical Mapping of an Origin of Bidirectional Replication at the Centre of the Borrelia Burgdorferi Linear Chromosome","volume":"32","author":"Picardeau","year":"1999","journal-title":"Mol. Microbiol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.abb.2007.09.023","article-title":"Zinc Is the Metal Cofactor of Borrelia Burgdorferi Peptide Deformylase","volume":"468","author":"Nguyen","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1073\/pnas.0812999106","article-title":"A Manganese Transporter, BB0219 (BmtA), Is Required for Virulence by the Lyme Disease Spirochete, Borrelia Burgdorferi","volume":"106","author":"Ouyang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_231","first-page":"141","article-title":"Insights into the Biology of Borrelia Burgdorferi Gained through the Application of Molecular Genetics","volume":"86","author":"Groshong","year":"2014","journal-title":"Adv. Appl. Microbiol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1126\/science.288.5471.1651","article-title":"Lack of a Role for Iron in the Lyme Disease Pathogen","volume":"288","author":"Posey","year":"2000","journal-title":"Science"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"19284","DOI":"10.1074\/jbc.M112.344903","article-title":"Borrelia Burgdorferi, a Pathogen That Lacks Iron, Encodes Manganese-Dependent Superoxide Dismutase Essential for Resistance to Streptonigrin","volume":"287","author":"Troxell","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"8468","DOI":"10.1074\/jbc.M112.433540","article-title":"A Manganese-Rich Environment Supports Superoxide Dismutase Activity in a Lyme Disease Pathogen, Borrelia Burgdorferi","volume":"288","author":"Aguirre","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3389\/fcimb.2013.00079","article-title":"Metal-Dependent Gene Regulation in the Causative Agent of Lyme Disease","volume":"3","author":"Troxell","year":"2013","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_236","unstructured":"Casjens, S., Eggers, C.H., and Schwartz, I. (2010). Borrelia Genomics: Chromosome, Plasmids, Bacteriophages and Genetic Variation. Borrelia: Molecular Biology, Host Interaction and Pathogenesis, Caister Academic Press."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ttbdis.2010.09.002","article-title":"Multilocus Sequence Analysis of Borrelia Bissettii Strains from North America Reveals a New Borrelia Species, Borrelia Kurtenbachii","volume":"1","author":"Margos","year":"2010","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1128\/JCM.01183-08","article-title":"Borrelia carolinensis Sp. Nov., a New (14th) Member of the Borrelia Burgdorferi Sensu Lato Complex from the Southeastern Region of the United States","volume":"47","author":"Rudenko","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1128\/JCM.01050-09","article-title":"Delineation of a New Species of the Borrelia Burgdorferi Sensu Lato Complex, Borrelia Americana Sp. Nov","volume":"47","author":"Rudenko","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1469-0691.2011.03492.x","article-title":"The Expanding Lyme Borrelia Complex\u2014Clinical Significance of Genomic Species?","volume":"17","author":"Stanek","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Lescot, M., Audic, S., Robert, C., Nguyen, T.T., Blanc, G., Cutler, S.J., Wincker, P., Couloux, A., Claverie, J.-M., and Raoult, D. (2008). The Genome of Borrelia Recurrentis, the Agent of Deadly Louse-Borne Relapsing Fever, Is a Degraded Subset of Tick-Borne Borrelia Duttonii. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000185"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Kuleshov, K.V., Margos, G., Fingerle, V., Koetsveld, J., Goptar, I.A., Markelov, M.L., Kolyasnikova, N.M., Sarksyan, D.S., Kirdyashkina, N.P., and Shipulin, G.A. (2020). Whole Genome Sequencing of Borrelia Miyamotoi Isolate Izh-4: Reference for a Complex Bacterial Genome. BMC Genom., 21.","DOI":"10.1186\/s12864-019-6388-4"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"4974","DOI":"10.1128\/JB.180.18.4974-4981.1998","article-title":"Cloning and Molecular Characterization of a Multicopy, Linear Plasmid-Carried, Repeat Motif-Containing Gene from Borrelia Turicatae, a Causative Agent of Relapsing Fever","volume":"180","author":"Carlyon","year":"1998","journal-title":"J. Bacteriol."},{"key":"ref_244","unstructured":"(2021). Genomics of Relapsing Fever Spirochetes. Lyme Disease and Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions and Disease Pathogenesis, Caister Academic Press."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.meegid.2014.04.022","article-title":"Phylogeny of a Relapsing Fever Borrelia Species Transmitted by the Hard Tick Ixodes Scapularis","volume":"27","author":"Barbour","year":"2014","journal-title":"Infect. Genet. Evol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"13865","DOI":"10.1073\/pnas.97.25.13865","article-title":"Correlation between Plasmid Content and Infectivity in Borrelia Burgdorferi","volume":"97","author":"Purser","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_247","first-page":"409","article-title":"Multipartite Genome of Lyme Disease Borrelia: Structure, Variation and Prophages","volume":"42","author":"Schwartz","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"A102","DOI":"10.1042\/bst028a102a","article-title":"The Unusual Linear Plasmids of the Lyme Disease Spirochete Borrelia Burgdorferi","volume":"28","author":"Casjens","year":"2000","journal-title":"Biochem. Soc. Transact."},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Casjens, S.R., Gilcrease, E.B., Vujadinovic, M., Mongodin, E.F., Luft, B.J., Schutzer, S.E., Fraser, C.M., and Qiu, W.-G. (2017). Plasmid Diversity and Phylogenetic Consistency in the Lyme Disease Agent Borrelia Burgdorferi. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3553-5"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.genet.37.040103.103949","article-title":"Pseudogenes: Are They \u201cJunk\u201d or Functional DNA?","volume":"37","author":"Balakirev","year":"2003","journal-title":"Annu. Rev. Genet."},{"key":"ref_251","doi-asserted-by":"crossref","unstructured":"Casjens, S.R., Di, L., Akther, S., Mongodin, E.F., Luft, B.J., Schutzer, S.E., Fraser, C.M., and Qiu, W.-G. (2018). Primordial Origin and Diversification of Plasmids in Lyme Disease Agent Bacteria. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4597-x"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1128\/IAI.00219-13","article-title":"Borrelia Burgdorferi Linear Plasmid 28-3 Confers a Selective Advantage in an Experimental Mouse-Tick Infection Model","volume":"81","author":"Dulebohn","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_253","doi-asserted-by":"crossref","unstructured":"Kobryn, K. (2021). Replication of the Borrelia Burgdorferi Genome. Lyme Disease and Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions and Disease Pathogenesis 2021, Caister Academic Press.","DOI":"10.21775\/9781913652616.04"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S1097-2765(01)00433-6","article-title":"ResT, a Telomere Resolvase Encoded by the Lyme Disease Spirochete","volume":"9","author":"Kobryn","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1128\/IAI.71.7.3699-3706.2003","article-title":"Linear and Circular Plasmid Content in Borrelia Burgdorferi Clinical Isolates","volume":"71","author":"Iyer","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1128\/IAI.68.7.3900-3908.2000","article-title":"The Relapsing Fever Spirochete Borrelia Hermsii Contains Multiple, Antigen-Encoding Circular Plasmids That Are Homologous to the cp32 Plasmids of Lyme Disease Spirochetes","volume":"68","author":"Stevenson","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_257","doi-asserted-by":"crossref","unstructured":"Tettelin, H., and Medini, D. (2020). The Bacterial Guide to Designing a Diversified Gene Portfolio. The Pangenome: Diversity, Dynamics and Evolution of Genomes, Springer International Publishing.","DOI":"10.1007\/978-3-030-38281-0"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"fnw296","DOI":"10.1093\/femsle\/fnw296","article-title":"Use of Pan-Genome Analysis for the Identification of Lineage-Specific Genes of Helicobacter Pylori","volume":"364","year":"2017","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"R103","DOI":"10.1186\/gb-2007-8-6-r103","article-title":"Characterization and Modeling of the Haemophilus Influenzae Core and Supragenomes Based on the Complete Genomic Sequences of Rd and 12 Clinical Nontypeable Strains","volume":"8","author":"Hogg","year":"2007","journal-title":"Genome Biol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1128\/JCM.00391-11","article-title":"Fourteen-Genome Comparison Identifies DNA Markers for Severe-Disease-Associated Strains of Clostridium Difficile","volume":"49","author":"Forgetta","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1111\/1462-2920.13732","article-title":"The Pangenome of the Genus Clostridium","volume":"19","author":"Udaondo","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1128\/jcm.35.12.3156-3162.1997","article-title":"Determination of Hepatitis C Virus Genotypes in the United States by Cleavase Fragment Length Polymorphism Analysis","volume":"35","author":"Marshall","year":"1997","journal-title":"J. Clin. Microbiol."},{"key":"ref_263","unstructured":"Rosenfeld, R., and Bluestone, C.D. (2003). Molecular and Translational Research Approaches for the Study of Bacterial Pathogenesis in Otitis Media. Evidence-Based Otitis Media, B.C. Decker Inc.. [2nd ed.]."},{"key":"ref_264","doi-asserted-by":"crossref","unstructured":"Ehrlich, G.D., Hu, F.Z., and Post, J.C. (2004). Role for Biofilms in Infectious Disease. Microbial Biofilms, American Society of Microbiology.","DOI":"10.1128\/9781555817718.ch18"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.1093\/nar\/gki670","article-title":"Codon Usage Comparison of Novel Genes in Clinical Isolates of Haemophilus Influenzae","volume":"33","author":"Gladitz","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1128\/IAI.73.6.3479-3491.2005","article-title":"Identification, Distribution, and Expression of Novel Genes in 10 Clinical Isolates of Nontypeable Haemophilus Influenzae","volume":"73","author":"Shen","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1128\/IAI.74.1.321-330.2006","article-title":"Characterization, Distribution, and Expression of Novel Genes among Eight Clinical Isolates of Streptococcus Pneumoniae","volume":"74","author":"Shen","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.3389\/fmicb.2018.03187","article-title":"Genome Sequencing and Pan-Genome Analysis of 23 Corallococcus spp. Strains Reveal Unexpected Diversity, With Particular Plasticity of Predatory Gene Sets","volume":"9","author":"Livingstone","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.3389\/fmicb.2018.03096","article-title":"The Core- and Pan-Genomic Analyses of the Genus Comamonas: From Environmental Adaptation to Potential Virulence","volume":"9","author":"Wu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1093\/gbe\/evw039","article-title":"Comparative Genomic Analyses of the Moraxella Catarrhalis Serosensitive and Seroresistant Lineages Demonstrate Their Independent Evolution","volume":"8","author":"Earl","year":"2016","journal-title":"Genome Biol. Evol."},{"key":"ref_271","unstructured":"Skovhus, T.L., Caffrey, S., and Hubert, C. (2014). Using the Core and Supra Genomes to Determine Diversity and Natural Proclivities among Bacterial Strains. Application of Molecular Microbiological Methods, Caister Academic Press."},{"key":"ref_272","doi-asserted-by":"crossref","unstructured":"Kress-Bennett, J.M., Hiller, N.L., Eutsey, R.A., Powell, E., Longwell, M.J., Hillman, T., Blackwell, T., Byers, B., Mell, J.C., and Post, J.C. (2016). Identification and Characterization of Msf, a Novel Virulence Factor in Haemophilus Influenzae. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149891"},{"key":"ref_273","doi-asserted-by":"crossref","unstructured":"Margos, G., Hepner, S., Mang, C., Marosevic, D., Reynolds, S.E., Krebs, S., Sing, A., Derdakova, M., Reiter, M.A., and Fingerle, V. (2017). Lost in Plasmids: Next Generation Sequencing and the Complex Genome of the Tick-Borne Pathogen Borrelia Burgdorferi. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3804-5"},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Mongodin, E.F., Casjens, S.R., Bruno, J.F., Xu, Y., Drabek, E.F., Riley, D.R., Cantarel, B.L., Pagan, P.E., Hernandez, Y.A., and Vargas, L.C. (2013). Inter- and Intra-Specific Pan-Genomes of Borrelia Burgdorferi Sensu Lato: Genome Stability and Adaptive Radiation. 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