{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:25:42Z","timestamp":1779927942942,"version":"3.53.1"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T00:00:00Z","timestamp":1489363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T00:00:00Z","timestamp":1489363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The causal agents of Lyme disease in North America,<jats:italic>Borrelia burgdorferi<\/jats:italic>and<jats:italic>Borrelia mayonii<\/jats:italic>, are transmitted primarily by<jats:italic>Ixodes scapularis<\/jats:italic>ticks. Due to their limited metabolic capacity, spirochetes rely on the tick blood meal for nutrients and metabolic intermediates while residing in the tick vector, competing with the tick for nutrients in the blood meal. Metabolomics is an effective methodology to explore dynamics of spirochete survival and multiplication in tick vectors before transmission to a vertebrate host via tick saliva. Using gas chromatography coupled to mass spectrometry, we identified statistically significant differences in the metabolic profile among uninfected<jats:italic>I. scapularis<\/jats:italic>nymphal ticks,<jats:italic>B. burgdorferi<\/jats:italic>-infected nymphal ticks and<jats:italic>B. mayonii<\/jats:italic>-infected nymphal ticks by measuring metabolism every 24\u2009hours over the course of their up to 96\u2009hour blood meals. Specifically, differences in the abundance of purines, amino acids, carbohydrates, and fatty acids during the blood meal among the three groups of nymphal ticks suggest that<jats:italic>B. mayonii<\/jats:italic>and<jats:italic>B. burgdorferi<\/jats:italic>may have different metabolic capabilities, especially during later stages of nymphal feeding. Understanding mechanisms underlying variable metabolic requirements of different Lyme disease spirochetes within tick vectors could potentially aid development of novel methods to control spirochete transmission.<\/jats:p>","DOI":"10.1038\/srep44394","type":"journal-article","created":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T13:42:33Z","timestamp":1489412553000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Metabolomics of the tick-Borrelia interaction during the nymphal tick blood meal"],"prefix":"10.1038","volume":"7","author":[{"given":"J. Charles","family":"Hoxmeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Fleshman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey D.","family":"Broeckling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica E.","family":"Prenni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc C.","family":"Dolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Gage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,13]]},"reference":[{"key":"BFsrep44394_CR1","doi-asserted-by":"crossref","unstructured":"Hinckley, A. F. et al. Lyme disease testing by large commercial laboratories in the United States. Clinical Infectious Diseases, ciu397 (2014).","DOI":"10.1093\/cid\/ciu397"},{"key":"BFsrep44394_CR2","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.idc.2015.02.010","volume":"29","author":"PS Mead","year":"2015","unstructured":"Mead, P. S. Epidemiology of Lyme disease. Infect Dis Clin N Am 29, 187\u2013210, doi: 10.1016\/j.idc.2015.02.010 (2015).","journal-title":"Infect Dis Clin N Am"},{"key":"BFsrep44394_CR3","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.3201\/eid2109.150417","volume":"21","author":"CA Nelson","year":"2015","unstructured":"Nelson, C. A. et al. Incidence of clinician-diagnosed Lyme disease, United States, 2005-2010. Emerg Infect Dis 21, 1625\u20131631, doi: 10.3201\/eid2109.150417 (2015).","journal-title":"Emerg Infect Dis"},{"key":"BFsrep44394_CR4","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1146\/annurev.ento.53.103106.093429","volume":"53","author":"J Piesman","year":"2008","unstructured":"Piesman, J. & Eisen, L. Prevention of tick-borne diseases. Ann Rev Entomol 53, 323\u2013343, doi: 10.1146\/annurev.ento.53.103106.093429 (2008).","journal-title":"Ann Rev Entomol"},{"key":"BFsrep44394_CR5","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1093\/jme\/tjv237","volume":"53","author":"RJ Eisen","year":"2016","unstructured":"Eisen, R. J., Eisen, L. & Beard, C. B. County-scale distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the continental United States. J Med Entomol 53, 349\u2013386, doi: 10.1093\/jme\/tjv237 (2016).","journal-title":"J Med Entomol"},{"key":"BFsrep44394_CR6","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.ttbdis.2016.02.012","volume":"7","author":"MC Dolan","year":"2016","unstructured":"Dolan, M. C. et al. Vector competence of the blacklegged tick, Ixodes scapularis, for the recently recognized Lyme borreliosis spirochete Candidatus Borrelia mayonii . Ticks Tick Borne Dis 7, 665\u2013669, doi: 10.1016\/j.ttbdis.2016.02.012 (2016).","journal-title":"Ticks Tick Borne Dis"},{"key":"BFsrep44394_CR7","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/s1473-3099(15)00464-8","volume":"16","author":"BS Pritt","year":"2016","unstructured":"Pritt, B. S. et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis 16, 556\u2013564, doi: 10.1016\/s1473-3099(15)00464-8 (2016).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep44394_CR8","doi-asserted-by":"crossref","unstructured":"Pritt, B. S. et al. Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States. Int J Syst Evol Microbiol, doi: 10.1099\/ijsem.0.001445 (2016).","DOI":"10.1099\/ijsem.0.001445"},{"key":"BFsrep44394_CR9","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.molbiopara.2010.09.008","volume":"175","author":"V Lakshmanan","year":"2011","unstructured":"Lakshmanan, V., Rhee, K. Y. & Daily, J. P. Metabolomics and malaria biology. Mol Biochem Parasitol 175, 104\u2013111, doi: 10.1016\/j.molbiopara.2010.09.008 (2011).","journal-title":"Mol Biochem Parasitol"},{"key":"BFsrep44394_CR10","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.chom.2010.01.008","volume":"7","author":"BF Kafsack","year":"2010","unstructured":"Kafsack, B. F. & Llinas, M. Eating at the table of another: metabolomics of host-parasite interactions. Cell Host Microbe 7, 90\u201399, doi: 10.1016\/j.chom.2010.01.008 (2010).","journal-title":"Cell Host Microbe"},{"key":"BFsrep44394_CR11","doi-asserted-by":"publisher","first-page":"e77283","DOI":"10.1371\/journal.pone.0077283","volume":"8","author":"LC Antunes","year":"2013","unstructured":"Antunes, L. C. et al. Metabolic signatures of triatomine vectors of Trypanosoma cruzi unveiled by metabolomics. PLoS One 8, e77283, doi: 10.1371\/journal.pone.0077283 (2013).","journal-title":"PLoS One"},{"issue":"4","key":"BFsrep44394_CR12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.5772\/5727","volume":"3","author":"Hatice Kose","year":"2006","unstructured":"de Andrade, J. B. et al. Perspectives for diagnosis and control of leishmaniasis based on volatile organic compounds. doi: 10.5772\/57279 (2014).","journal-title":"International Journal of Advanced Robotic Systems"},{"key":"BFsrep44394_CR13","doi-asserted-by":"publisher","first-page":"9242","DOI":"10.1038\/srep09242","volume":"5","author":"JC Hoxmeier","year":"2015","unstructured":"Hoxmeier, J. C. et al. Analysis of the metabolome of Anopheles gambiae mosquito after exposure to Mycobacterium ulcerans . Sci Rep 5, 9242, doi: 10.1038\/srep09242 (2015).","journal-title":"Sci Rep"},{"key":"BFsrep44394_CR14","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1093\/cid\/civ185","volume":"60","author":"CR Molins","year":"2015","unstructured":"Molins, C. R. et al. Development of a metabolic biosignature for detection of early Lyme disease. Clin Infect Dis 60, 1767\u20131775, doi: 10.1093\/cid\/civ185 (2015).","journal-title":"Clin Infect Dis"},{"key":"BFsrep44394_CR15","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1111\/cmi.12609","volume":"18","author":"MJ Caimano","year":"2016","unstructured":"Caimano, M. J., Drecktrah, D., Kung, F. & Samuels, D. S. Interaction of the Lyme disease spirochete with its tick vector. Cell Microbiol 18, 919\u2013927, doi: 10.1111\/cmi.12609 (2016).","journal-title":"Cell Microbiol"},{"key":"BFsrep44394_CR16","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/pca.2505","volume":"25","author":"MY Mushtaq","year":"2014","unstructured":"Mushtaq, M. Y., Choi, Y. H., Verpoorte, R. & Wilson, E. G. Extraction for metabolomics: access to the metabolome. Phytochem Anal 25, 291\u2013306, doi: 10.1002\/pca.2505 (2014).","journal-title":"Phytochem Anal"},{"key":"BFsrep44394_CR17","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1007\/s00216-014-8127-7","volume":"407","author":"P Gao","year":"2015","unstructured":"Gao, P. & Xu, G. Mass-spectrometry-based microbial metabolomics: recent developments and applications. Anal Bioanal Chem 407, 669\u2013680, doi: 10.1007\/s00216-014-8127-7 (2015).","journal-title":"Anal Bioanal Chem"},{"key":"BFsrep44394_CR18","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrm3314","volume":"13","author":"GJ Patti","year":"2012","unstructured":"Patti, G. J., Yanes, O. & Siuzdak, G. Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 13, 263\u2013269, doi: 10.1038\/nrm3314 (2012).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFsrep44394_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s11306-005-1102-8","volume":"1","author":"JB German","year":"2005","unstructured":"German, J. B., Hammock, B. D. & Watkins, S. M. Metabolomics: building on a century of biochemistry to guide human health. Metabolomics 1, 3\u20139, doi: 10.1007\/s11306-005-1102-8 (2005).","journal-title":"Metabolomics"},{"key":"BFsrep44394_CR20","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1126\/science.276.5313.718","volume":"276","author":"BB Finlay","year":"1997","unstructured":"Finlay, B. B. & Cossart, P. Exploitation of mammalian host cell functions by bacterial pathogens. Science 276, 718\u2013725, doi: 10.1126\/science.276.5313.718 (1997).","journal-title":"Science"},{"key":"BFsrep44394_CR21","unstructured":"Gherardini, F., Boylan, J., Lawrence, K. & Skare, J. In Borrelia: molecular biology, host interaction and pathogenesis (ed. Justin D. Radolf ) 103\u2013138 (2010)."},{"key":"BFsrep44394_CR22","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/37551","volume":"390","author":"CM Fraser","year":"1997","unstructured":"Fraser, C. M. et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi . Nature 390, 580\u2013586, doi: 10.1038\/37551 (1997).","journal-title":"Nature"},{"key":"BFsrep44394_CR23","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.idc.2007.12.013","volume":"22","author":"K Tilly","year":"2008","unstructured":"Tilly, K., Rosa, P. A. & Stewart, P. E. Biology of infection with Borrelia burgdorferi . Infect Dis Clin North Am 22, 217\u2013234, v, doi: 10.1016\/j.idc.2007.12.013 (2008).","journal-title":"Infect Dis Clin North Am"},{"key":"BFsrep44394_CR24","unstructured":"Sonenshine, D. Biology of ticks, vol. II. (Oxford University Press, New York, NY, 1993)."},{"key":"BFsrep44394_CR25","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1111\/mmi.12882","volume":"95","author":"R Iyer","year":"2015","unstructured":"Iyer, R. et al. Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation. Molec Microbiol 95, 509\u2013538, doi: 10.1111\/mmi.12882 (2015).","journal-title":"Molec Microbiol"},{"key":"BFsrep44394_CR26","unstructured":"Pal, U. & Fikrig, E. In Borrelia: molecular biology, host interaction and pathogenesis (ed. Samuels, D. S., Radolf, J. D. ) 279\u2013298 (Caister Academic, 2010)."},{"key":"BFsrep44394_CR27","doi-asserted-by":"publisher","first-page":"4145","DOI":"10.1128\/JCM.39.11.4145-4148.2001","volume":"39","author":"J Piesman","year":"2001","unstructured":"Piesman, J., Schneider, B. S. & Zeidner, N. S. Use of quantitative PCR to measure density of Borrelia burgdorferi in the midgut and salivary glands of feeding tick vectors. J Clin Microbiol 39, 4145\u20134148 (2001).","journal-title":"J Clin Microbiol"},{"key":"BFsrep44394_CR28","doi-asserted-by":"publisher","first-page":"3652","DOI":"10.1172\/JCI39401","volume":"119","author":"SM Dunham-Ems","year":"2009","unstructured":"Dunham-Ems, S. M. et al. Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks. J Clin Invest 119, 3652\u20133665 (2009).","journal-title":"J Clin Invest"},{"key":"BFsrep44394_CR29","doi-asserted-by":"publisher","first-page":"352","DOI":"10.4269\/ajtmh.1990.42.352","volume":"42","author":"J Piesman","year":"1990","unstructured":"Piesman, J., Oliver, J. R. & Sinsky, R. J. Growth kinetics of the Lyme disease spirochete (Borrelia burgdorferi) in vector ticks (Ixodes dammini). Am J Trop Med Hyg 42, 352\u2013357 (1990).","journal-title":"Am J Trop Med Hyg"},{"key":"BFsrep44394_CR30","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.femsle.2004.12.002","volume":"243","author":"K von Lackum","year":"2005","unstructured":"von Lackum, K. & Stevenson, B. Carbohydrate utilization by the Lyme borreliosis spirochete, Borrelia burgdorferi . FEMS Microbiol Lett 243, 173\u2013179, doi: 10.1016\/j.femsle.2004.12.002 (2005).","journal-title":"FEMS Microbiol Lett"},{"key":"BFsrep44394_CR31","doi-asserted-by":"publisher","first-page":"e38171","DOI":"10.1371\/journal.pone.0038171","volume":"7","author":"TA Van Laar","year":"2012","unstructured":"Van Laar, T. A. et al. Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi . PLoS One 7, e38171, doi: 10.1371\/journal.pone.0038171 (2012).","journal-title":"PLoS One"},{"key":"BFsrep44394_CR32","doi-asserted-by":"publisher","first-page":"e1001104","DOI":"10.1371\/journal.ppat.1001104","volume":"6","author":"H Xu","year":"2010","unstructured":"Xu, H. et al. Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi . PLoS Pathog 6, e1001104, doi: 10.1371\/journal.ppat.1001104 (2010).","journal-title":"PLoS Pathog"},{"key":"BFsrep44394_CR33","doi-asserted-by":"publisher","first-page":"e1002102","DOI":"10.1371\/journal.ppat.1002102","volume":"7","author":"CJ Pappas","year":"2011","unstructured":"Pappas, C. J. et al. Borrelia burgdorferi requires glycerol for maximum fitness during the tick phase of the enzootic cycle. PLoS Pathog 7, e1002102, doi: 10.1371\/journal.ppat.1002102 (2011).","journal-title":"PLoS Pathog"},{"key":"BFsrep44394_CR34","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.1128\/IAI.00199-07","volume":"75","author":"J Pettersson","year":"2007","unstructured":"Pettersson, J. et al. Purine salvage pathways among Borrelia species. Infect Immun 75, 3877\u20133884, doi: 10.1128\/IAI.00199-07 (2007).","journal-title":"Infect Immun"},{"key":"BFsrep44394_CR35","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/jmedent\/30.1.199","volume":"30","author":"J Piesman","year":"1993","unstructured":"Piesman, J. Standard system for infecting ticks (Acari: Ixodidae) with the Lyme disease spirochete, Borrelia burgdorferi . J Med Entomol 30, 199\u2013203 (1993).","journal-title":"J Med Entomol"},{"issue":"5","key":"BFsrep44394_CR36","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/S1473-3099(15)00464-8","volume":"16","author":"Bobbi S Pritt","year":"2016","unstructured":"Pritt, B. S. et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis, doi: 10.1016\/S1473-3099(15)00464-8.","journal-title":"The Lancet Infectious Diseases"},{"key":"BFsrep44394_CR37","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.4269\/ajtmh.2011.11-0292","volume":"85","author":"MC Dolan","year":"2011","unstructured":"Dolan, M. C. et al. Elimination of Borrelia burgdorferi and Anaplasma phagocytophilum in rodent reservoirs and Ixodes scapularis ticks using a doxycycline hyclate-laden bait. Am J Trop Med Hyg 85, 1114\u20131120, doi: 10.4269\/ajtmh.2011.11-0292 (2011).","journal-title":"Am J Trop Med Hyg"},{"key":"BFsrep44394_CR38","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1093\/jme\/tju005","volume":"52","author":"J Goddard","year":"2015","unstructured":"Goddard, J., Embers, M., Hojgaard, A. & Piesman, J. Comparison of tick feeding success and vector competence for Borrelia burgdorferi among immature Ixodes scapularis (Ixodida: Ixodidae) of both southern and northern clades. J Med Entomol 52, 81\u201385, doi: 10.1093\/jme\/tju005 (2015).","journal-title":"J Med Entomol"},{"key":"BFsrep44394_CR39","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.ttbdis.2013.12.001","volume":"5","author":"A Hojgaard","year":"2014","unstructured":"Hojgaard, A., Lukacik, G. & Piesman, J. Detection of Borrelia burgdorferi, Anaplasma phagocytophilum and Babesia microti, with two different multiplex PCR assays. Ticks Tick Borne Dis 5, 349\u2013351, doi: 10.1016\/j.ttbdis.2013.12.001 (2014).","journal-title":"Ticks Tick Borne Dis"},{"key":"BFsrep44394_CR40","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1021\/ac051437y","volume":"78","author":"CA Smith","year":"2006","unstructured":"Smith, C. A., Want, E. J., O\u2019Maille, G., Abagyan, R. & Siuzdak, G. XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem 78, 779\u2013787, doi: 10.1021\/ac051437y (2006).","journal-title":"Anal Chem"},{"key":"BFsrep44394_CR41","doi-asserted-by":"publisher","first-page":"6812","DOI":"10.1021\/ac501530d","volume":"86","author":"CD Broeckling","year":"2014","unstructured":"Broeckling, C. D., Afsar, F. A., Neumann, S., Ben-Hur, A. & Prenni, J. E. RAMClust: A novel feature clustering method enables spectral-matching-based annotation for metabolomics data. Anal Chem 86, 6812\u20136817, doi: 10.1021\/ac501530d (2014).","journal-title":"Anal Chem"},{"key":"BFsrep44394_CR42","doi-asserted-by":"crossref","unstructured":"Broeckling, C. D. et al. Annotation from the MS1-spectrum and time predictions approach to LC-MS metabolomics data. Anal Chem, doi: 10.1021\/acs.analchem.6b02479 (2016).","DOI":"10.1021\/acs.analchem.6b02479"},{"key":"BFsrep44394_CR43","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","volume":"3","author":"LW Sumner","year":"2007","unstructured":"Sumner, L. W. et al. Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics 3, 211\u2013221, doi: 10.1007\/s11306-007-0082-2 (2007).","journal-title":"Metabolomics"},{"key":"BFsrep44394_CR44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57, 289\u2013300 (1995).","journal-title":"J R Stat Soc B"},{"key":"BFsrep44394_CR45","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.jfda.2015.02.008","volume":"23","author":"TA Wani","year":"2015","unstructured":"Wani, T. A. & Zargar, S. New ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of irbesartan in human plasma. J Food Drug Anal 23, 569\u2013576, doi: 10.1016\/j.jfda.2015.02.008 (2015).","journal-title":"J Food Drug Anal"},{"key":"BFsrep44394_CR46","doi-asserted-by":"crossref","unstructured":"Berens, R. L., Krug, E. C. & Marr, J. J. In Biochemistry and Molecular Biology of Parasites (ed. Marr, J. & Muller, M. ) 89\u2013117 (1995).","DOI":"10.1016\/B978-012473345-9\/50007-6"},{"key":"BFsrep44394_CR47","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.1128\/IAI.00514-12","volume":"80","author":"S Jain","year":"2012","unstructured":"Jain, S., Sutchu, S., Rosa, P. A., Byram, R. & Jewett, M. W. Borrelia burgdorferi harbors a transport system essential for purine salvage and mammalian infection. Infect Immun 80, 3086\u20133093, doi: 10.1128\/IAI.00514-12 (2012).","journal-title":"Infect Immun"},{"key":"BFsrep44394_CR48","doi-asserted-by":"publisher","first-page":"6231","DOI":"10.1128\/JB.00450-09","volume":"191","author":"MW Jewett","year":"2009","unstructured":"Jewett, M. W. et al. GuaA and GuaB are essential for Borrelia burgdorferi survival in the tick-mouse infection cycle. J Bacteriol 191, 6231\u20136241, doi: 10.1128\/JB.00450-09 (2009).","journal-title":"J Bacteriol"},{"key":"BFsrep44394_CR49","doi-asserted-by":"publisher","first-page":"6427","DOI":"10.1128\/jb.176.21.6427-6432.1994","volume":"176","author":"N Margolis","year":"1994","unstructured":"Margolis, N., Hogan, D., Tilly, K. & Rosa, P. A. Plasmid location of Borrelia purine biosynthesis gene homologs. J Bacteriol 176, 6427\u20136432 (1994).","journal-title":"J Bacteriol"},{"key":"BFsrep44394_CR50","doi-asserted-by":"publisher","first-page":"5189","DOI":"10.1073\/pnas.83.14.5189","volume":"83","author":"PI Fields","year":"1986","unstructured":"Fields, P. I., Swanson, R. V., Haidaris, C. G. & Heffron, F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci USA 83, 5189\u20135193 (1986).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep44394_CR51","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0021-9673(00)95286-5","volume":"186","author":"RA Hartwick","year":"1979","unstructured":"Hartwick, R. A., Krstulovic, A. M. & Brown, P. R. Identification and quantitation of nucleosides, bases and other UV-absorbing compounds in serum, using reversed-phase high-performance liquid chromatography. II. Evaluation of human sera. J Chromatogr 186, 659\u2013676 (1979).","journal-title":"Evaluation of human sera. J Chromatogr"},{"key":"BFsrep44394_CR52","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/S0092-8674(02)00665-7","volume":"108","author":"NA Moran","year":"2002","unstructured":"Moran, N. A. Microbial minimalism: genome reduction in bacterial pathogens. Cell 108, 583\u2013586, doi: 10.1016\/S0092-8674(02)00665-7 (2002).","journal-title":"Cell"},{"key":"BFsrep44394_CR53","first-page":"265","volume":"55","author":"IW Sherman","year":"1977","unstructured":"Sherman, I. W. Amino acid metabolism and protein synthesis in malarial parasites. Bull World Health Organ 55, 265 (1977).","journal-title":"Bull World Health Organ"},{"key":"BFsrep44394_CR54","unstructured":"Johnson, R. C. Biology of parasitic spirochaetes. (Academic Press, 2013)."},{"key":"BFsrep44394_CR55","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.pt.2007.02.004","volume":"23","author":"FR Opperdoes","year":"2007","unstructured":"Opperdoes, F. R. & Coombs, G. H. Metabolism of Leishmania: proven and predicted. Trends Parasitol 23, 149\u2013158, doi: 10.1016\/j.pt.2007.02.004 (2007).","journal-title":"Trends Parasitol"},{"key":"BFsrep44394_CR56","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.mib.2012.02.003","volume":"15","author":"I Chouikha","year":"2012","unstructured":"Chouikha, I. & Hinnebusch, B. J. Yersinia\u2013flea interactions and the evolution of the arthropod-borne transmission route of plague. Curr Opin Microbiol 15, 239\u2013246, doi: 10.1016\/j.mib.2012.02.003 (2012).","journal-title":"Curr Opin Microbiol"},{"key":"BFsrep44394_CR57","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/j.1574-695X.2012.00996.x","volume":"66","author":"LL Hoon-Hanks","year":"2012","unstructured":"Hoon-Hanks, L. L. et al. Borrelia burgdorferi malQ mutants utilize disaccharides and traverse the enzootic cycle. FEMS Immunol Med Microbiol 66, 157\u2013165, doi: 10.1111\/j.1574-695X.2012.00996.x (2012).","journal-title":"FEMS Immunol Med Microbiol"},{"key":"BFsrep44394_CR58","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1099\/00207713-34-4-496","volume":"34","author":"RC Johnson","year":"1984","unstructured":"Johnson, R. C., Schmid, G. P., Hyde, F. W., Steigerwalt, A. & Brenner, D. J. Borrelia burgdorferi sp. nov.: etiologic agent of Lyme disease. Int J Sys Bacteriol 34, 496\u2013497 (1984).","journal-title":"Int J Sys Bacteriol"},{"key":"BFsrep44394_CR59","doi-asserted-by":"crossref","unstructured":"Troy, E. B. et al. Global Tn-seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi . Mol Microbiol, doi: 10.1111\/mmi.13437 (2016).","DOI":"10.1111\/mmi.13437"},{"key":"BFsrep44394_CR60","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/clinchem\/17.5.403","volume":"17","author":"DS Young","year":"1971","unstructured":"Young, D. S., Harris, E. K. & Cotlove, E. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. IV. Results of a study designed to eliminate long-term analytic deviations. Clin Chem 17, 403\u2013410 (1971).","journal-title":"Clin Chem"},{"key":"BFsrep44394_CR61","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1128\/iai.00917-15","volume":"84","author":"BK Khajanchi","year":"2016","unstructured":"Khajanchi, B. K. et al. Phosphoenolpyruvate phosphotransferase system components modulate gene transcription and virulence of Borrelia burgdorferi . Infect and Immun 84, 754\u2013764, doi: 10.1128\/iai.00917-15 (2016).","journal-title":"Infect and Immun"},{"key":"BFsrep44394_CR62","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1111\/j.1365-2958.2007.05947.x","volume":"66","author":"Y Fujita","year":"2007","unstructured":"Fujita, Y., Matsuoka, H. & Hirooka, K. Regulation of fatty acid metabolism in bacteria. Mol Microbiol 66, 829\u2013839, doi: 10.1111\/j.1365-2958.2007.05947.x (2007).","journal-title":"Mol Microbiol"},{"key":"BFsrep44394_CR63","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1111\/j.1462-5822.2012.01794.x","volume":"14","author":"CA Elwell","year":"2012","unstructured":"Elwell, C. A. & Engel, J. N. Lipid acquisition by intracellular Chlamydiae . Cell Microbiol 14, 1010\u20131018, doi: 10.1111\/j.1462-5822.2012.01794.x (2012).","journal-title":"Cell Microbiol"},{"key":"BFsrep44394_CR64","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1111\/j.1462-5822.2005.00641.x","volume":"8","author":"D Howe","year":"2006","unstructured":"Howe, D. & Heinzen, R. A. Coxiella burnetii inhabits a cholesterol-rich vacuole and influences cellular cholesterol metabolism. Cell Microbiol 8, 496\u2013507, doi: 10.1111\/j.1462-5822.2005.00641.x (2006).","journal-title":"Cell Microbiol"},{"key":"BFsrep44394_CR65","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/0005-2760(69)90030-7","volume":"187","author":"CL Randle","year":"1969","unstructured":"Randle, C. L., Albro, P. W. & Dittmer, J. C. The phosphoglyceride composition of Gram-negative bacteria and the changes in composition during growth. Biochim Biophys Acta 187, 214\u2013220 (1969).","journal-title":"Biochim Biophys Acta"},{"key":"BFsrep44394_CR66","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.1016\/S0021-9258(20)81908-5","volume":"258","author":"TJ Larson","year":"1983","unstructured":"Larson, T. J., Ehrmann, M. & Boos, W. Periplasmic glycerophosphodiester phosphodiesterase of Escherichia coli, a new enzyme of the glp regulon. J Biol Chem 258, 5428\u20135432 (1983).","journal-title":"J Biol Chem"},{"key":"BFsrep44394_CR67","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/254150a0","volume":"254","author":"GW Chang","year":"1975","unstructured":"Chang, G. W. & Chang, J. T. Evidence for the B12-dependent enzyme ethanolamine deaminase in Salmonella. Nature 254, 150\u2013151 (1975).","journal-title":"Nature"},{"key":"BFsrep44394_CR68","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1042\/bst0040495","volume":"4","author":"CM Blackwell","year":"1976","unstructured":"Blackwell, C. M., Scarlett, F. A. & Turner, J. M. Ethanolamine catabolism by bacteria, including Escherichia coli . Biochem Soc Trans 4, 495\u2013497 (1976).","journal-title":"Biochem Soc Trans"},{"key":"BFsrep44394_CR69","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/j.1462-2920.2010.02334.x","volume":"13","author":"Y Bertin","year":"2011","unstructured":"Bertin, Y. et al. Enterohaemorrhagic Escherichia coli gains a competitive advantage by using ethanolamine as a nitrogen source in the bovine intestinal content. Environ Microbiol 13, 365\u2013377, doi: 10.1111\/j.1462-2920.2010.02334.x (2011).","journal-title":"Environ Microbiol"},{"key":"BFsrep44394_CR70","doi-asserted-by":"publisher","first-page":"7147","DOI":"10.1128\/jb.00952-08","volume":"190","author":"MF Del Papa","year":"2008","unstructured":"Del Papa, M. F. & Perego, M. Ethanolamine activates a sensor histidine kinase regulating its utilization in Enterococcus faecalis . J Bacteriol 190, 7147\u20137156, doi: 10.1128\/jb.00952-08 (2008).","journal-title":"J Bacteriol"},{"key":"BFsrep44394_CR71","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nrmicro2334","volume":"8","author":"DA Garsin","year":"2010","unstructured":"Garsin, D. A. Ethanolamine utilization in bacterial pathogens: roles and regulation. Nat Rev Microbiol 8, 290\u2013295, doi: 10.1038\/nrmicro2334 (2010).","journal-title":"Nat Rev Microbiol"},{"key":"BFsrep44394_CR72","doi-asserted-by":"publisher","first-page":"e1005278","DOI":"10.1371\/journal.ppat.1005278","volume":"11","author":"CJ Anderson","year":"2015","unstructured":"Anderson, C. J., Clark, D. E., Adli, M. & Kendall, M. M. Ethanolamine signaling promotes Salmonella niche recognition and adaptation during infection. PLoS Pathog 11, e1005278, doi: 10.1371\/journal.ppat.1005278 (2015).","journal-title":"PLoS Pathog"},{"key":"BFsrep44394_CR73","doi-asserted-by":"publisher","first-page":"89","DOI":"10.15698\/mic2016.02.479","volume":"3","author":"CJ Anderson","year":"2016","unstructured":"Anderson, C. J., Clark, D. E., Adli, M. & Kendall, M. M. Salmonella senses ethanolamine to gauge distinct host environments and coordinate gene expression. Microbial Cell 3, 89\u201391, doi: 10.15698\/mic2016.02.479 (2016).","journal-title":"Microbial Cell"},{"key":"BFsrep44394_CR74","doi-asserted-by":"crossref","unstructured":"Kendall, M. M., Gruber, C. C., Parker, C. T. & Sperandio, V. Ethanolamine controls expression of genes encoding components involved in interkingdom signaling and virulence in enterohemorrhagic Escherichia coli O157:H7. mBio 3, doi: 10.1128\/mBio.00050-12 (2012).","DOI":"10.1128\/mBio.00050-12"},{"key":"BFsrep44394_CR75","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1128\/AEM.01403-10","volume":"77","author":"S Srikumar","year":"2011","unstructured":"Srikumar, S. & Fuchs, T. M. Ethanolamine utilization contributes to proliferation of Salmonella enterica serovar Typhimurium in food and in nematodes. Appl Environ Microbiol 77, 281\u2013290, doi: 10.1128\/AEM.01403-10 (2011).","journal-title":"Appl Environ Microbiol"},{"key":"BFsrep44394_CR76","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1128\/iai.20.1.215-220.1978","volume":"20","author":"BP Livermore","year":"1978","unstructured":"Livermore, B. P., Bey, R. F. & Johnson, R. C. Lipid metabolism of Borrelia hermsi . Infect Immun 20, 215\u2013220 (1978).","journal-title":"Infect Immun"},{"key":"BFsrep44394_CR77","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1146\/annurev.mi.31.100177.000513","volume":"31","author":"RC Johnson","year":"1977","unstructured":"Johnson, R. C. The spirochetes. Annu Rev in Microbiol 31, 89\u2013106 (1977).","journal-title":"The spirochetes. Annu Rev in Microbiol"},{"key":"BFsrep44394_CR78","doi-asserted-by":"publisher","first-page":"e1003109","DOI":"10.1371\/journal.ppat.1003109","volume":"9","author":"JT Crowley","year":"2013","unstructured":"Crowley, J. T. et al. Lipid exchange between Borrelia burgdorferi and host cells. PLoS Pathog 9, e1003109, doi: 10.1371\/journal.ppat.1003109 (2013).","journal-title":"PLoS Pathog"},{"key":"BFsrep44394_CR79","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1128\/jb.176.8.2151-2157.1994","volume":"176","author":"JT Belisle","year":"1994","unstructured":"Belisle, J. T., Brandt, M. E., Radolf, J. D. & Norgard, M. V. Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins. J Bacteriol 176, 2151\u20132157 (1994).","journal-title":"J Bacteriol"},{"key":"BFsrep44394_CR80","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1128\/iai.63.6.2154-2163.1995","volume":"63","author":"JD Radolf","year":"1995","unstructured":"Radolf, J. D. et al. Characterization of outer membranes isolated from Borrelia burgdorferi, the Lyme disease spirochete. Infect and Immun 63, 2154\u20132163 (1995).","journal-title":"Infect and Immun"},{"key":"BFsrep44394_CR81","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/S0300-9084(01)01296-2","volume":"83","author":"H Hossain","year":"2001","unstructured":"Hossain, H., Wellensiek, H.-J., Geyer, R. & Lochnit, G. Structural analysis of glycolipids from Borrelia burgdorferi . Biochimie 83, 683\u2013692, doi: 10.1016\/S0300-9084(01)01296-2 (2001).","journal-title":"Biochimie"},{"key":"BFsrep44394_CR82","doi-asserted-by":"publisher","first-page":"e1003353","DOI":"10.1371\/journal.ppat.1003353","volume":"9","author":"TJ LaRocca","year":"2013","unstructured":"LaRocca, T. J. et al. Proving lipid rafts exist: membrane domains in the prokaryote Borrelia burgdorferi have the same properties as eukaryotic lipid rafts. PLoS Pathog 9, e1003353 (2013).","journal-title":"PLoS Pathog"},{"key":"BFsrep44394_CR83","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.chom.2010.09.001","volume":"8","author":"TJ LaRocca","year":"2010","unstructured":"LaRocca, T. J. et al. Cholesterol lipids of Borrelia burgdorferi form lipid rafts and are required for the bactericidal activity of a complement-independent antibody. Cell Host Microbe 8, 331\u2013342, doi: 10.1016\/j.chom.2010.09.001 (2010).","journal-title":"Cell Host Microbe"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep44394.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep44394","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep44394.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T19:16:52Z","timestamp":1750101412000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep44394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,13]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,6,1]]}},"alternative-id":["BFsrep44394"],"URL":"https:\/\/doi.org\/10.1038\/srep44394","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,13]]},"assertion":[{"value":"10 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"44394"}}