{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:26Z","timestamp":1787028926677,"version":"build-2736575974"},"reference-count":109,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Linkou Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3K2421;CMRPG3L0791"],"award-info":[{"award-number":["CMRPG3K2421;CMRPG3L0791"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 110-2314-B-182A-017"],"award-info":[{"award-number":["MOST 110-2314-B-182A-017"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Leptospirosis is a widespread zoonosis that frequently occurs in tropical and subtropical countries. Leptospira enters the host through wounds or mucous membranes and spreads to the whole body through the blood, causing systemic infection. Kidneys are the preferential site where Leptospira accumulates, especially in the renal interstitium and renal tubule epithelial cells. Clinical symptoms in humans include high fever, jaundice, renal failure, and severe multiple-organ failure (Weil\u2019s syndrome). Surface-exposed antigens are located at the outermost layer of Leptospira and these potential virulence factors are likely involved in primary host-pathogen interactions, adhesion, and\/or invasion. Using the knockout\/knockdown techniques to the evaluation of pathogenicity in the virulence factor are the most direct and effective methods and many virulence factors are evaluated including lipopolysaccharides (LPS), Leptospira lipoprotein 32 (LipL32), Leptospira ompA domain protein 22 (Loa22), LipL41, LipL71, Leptospira immunoglobulin-like repeat A (LigA), LigB, and LipL21. In this review, we will discuss the structure, functions, and dynamics of these virulence factors and the roles of these virulence factors in Leptospira pathogenicity. In addition, a protein family with special Leucine-rich repeat (LRR) will also be discussed for their vital role in Leptospira pathogenicity. Finally, these surface-exposed antigens are discussed in the application of the diagnosis target for leptospirosis and compared with the serum microscope agglutination test (MAT), the gold standard for leptospirosis.<\/jats:p>","DOI":"10.3390\/membranes12030300","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T10:21:16Z","timestamp":1646648476000},"page":"300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Insight into the Structure, Functions, and Dynamics of the Leptospira Outer Membrane Proteins with the Pathogenicity"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-4151","authenticated-orcid":false,"given":"Shen-Hsing","family":"Hsu","sequence":"first","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 5 Fu-Shing St., Taoyuan 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S1473-3099(03)00830-2","article-title":"Leptospirosis: A zoonotic disease of global importance","volume":"3","author":"Bharti","year":"2003","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.vetmic.2009.03.012","article-title":"Leptospira and leptospirosis","volume":"140","author":"Adler","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_3","first-page":"295","article-title":"Leptospirosis: Public health perspectives","volume":"41","author":"Guerra","year":"2013","journal-title":"Biol. J. Int. Assoc. Biol. Stand."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1620\/tjem.238.287","article-title":"Development of point-of-care testing for disaster-related infectious diseases","volume":"238","author":"Hattori","year":"2016","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yang, C.W. (2017). Leptospirosis renal disease: Emerging culprit of chronic kidney disease unknown etiology. Nephron, 138.","DOI":"10.1159\/000480691"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinf.2009.05.005","article-title":"Fever in returned travellers presenting in the United Kingdom: Recommendations for investigation and initial management","volume":"59","author":"Johnston","year":"2009","journal-title":"J. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/sj.ki.5002393","article-title":"Leptospirosis renal disease: Understanding the initiation by Toll-like receptors","volume":"72","author":"Yang","year":"2007","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Costa, F., Hagan, J.E., Calcagno, J., Kane, M., Torgerson, P., Martinez-Silveira, M.S., Stein, C., Abela-Ridder, B., and Ko, A.I. (2015). Global morbidity and mortality of leptospirosis: A systematic review. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003898"},{"key":"ref_9","first-page":"109","article-title":"Leptospirosis in Taiwan\u2014An underestimated infectious disease","volume":"30","author":"Yang","year":"2007","journal-title":"Chang. Gung Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sharp, T.M., Rivera Garcia, B., Perez-Padilla, J., Galloway, R.L., Guerra, M., Ryff, K.R., Haberling, D., Ramakrishnan, S., Shadomy, S., and Blau, D. (2016). Early Indicators of Fatal Leptospirosis during the 2010 Epidemic in Puerto Rico. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004482"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, H.Y., Hung, C.C., Liu, S.H., Guo, Y.G., Chen, Y.C., Ko, Y.C., Huang, C.T., Chou, L.F., Tian, Y.C., and Chang, M.Y. (2015). Overlooked risk for chronic kidney disease after leptospiral infection: A population-based survey and epidemiological cohort evidence. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004105"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fcimb.2018.00204","article-title":"Leptospirosis pathophysiology: Into the storm of cytokines","volume":"8","author":"Cagliero","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Senavirathna, I., Rathish, D., and Agampodi, S. (2020). Cytokine response in human leptospirosis with different clinical outcomes: A systematic review. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-04986-9"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dickson, K., and Lehmann, C. (2019). Inflammatory response to different toxins in experimental sepsis models. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184341"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.vetimm.2015.12.004","article-title":"Leptospira spp.: Novel insights into host-pathogen interactions","volume":"176","author":"Fernandes","year":"2016","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/1040841X.2020.1735299","article-title":"The interplay between host haemostatic systems and Leptospira spp. infections","volume":"46","author":"Vieira","year":"2020","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"777709","DOI":"10.3389\/fcimb.2021.777709","article-title":"A review on host-Leptospira Interactions: What we know and future expectations","volume":"11","author":"Daroz","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-3-662-45059-8_5","article-title":"Leptospirosis in humans","volume":"387","author":"Haake","year":"2015","journal-title":"Leptospira Leptospirosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/ndt\/16.suppl_5.73","article-title":"Leptospirosis renal disease","volume":"16","author":"Yang","year":"2001","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1099\/00221287-146-7-1491","article-title":"Spirochaetal lipoproteins and pathogenesis","volume":"146","author":"Haake","year":"2000","journal-title":"Microbiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/j.1348-0421.1987.tb03134.x","article-title":"Biological activities of lipopolysaccharide-like substance (LLS) extracted from Leptospira interrogans serovar canicola strain Moulton","volume":"31","author":"Shimizu","year":"1987","journal-title":"Microbiol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide endotoxins","volume":"71","author":"Raetz","year":"2002","journal-title":"Annu Rev. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/86354","article-title":"Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism","volume":"2","author":"Werts","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_24","first-page":"193","article-title":"Bagshaped macromolecules-a new outlook on bacterial cell walls","volume":"26","author":"Weidel","year":"1964","journal-title":"Adv. Enzym. Relat. Subj. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/jmm.0.000636","article-title":"Cell-wall recycling and synthesis in Escherichia coli and Pseudomonas aeruginosa\u2014Their role in the development of resistance","volume":"67","author":"Dhar","year":"2018","journal-title":"J. Med. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1093\/ndt\/gfi316","article-title":"Leptospiral membrane proteins stimulate pro-inflammatory chemokines secretion by renal tubule epithelial cells through toll-like receptor 2 and p38 mitogen activated protein kinase","volume":"21","author":"Hung","year":"2006","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.femsre.2003.10.004","article-title":"Outer membrane proteins of pathogenic spirochetes","volume":"28","author":"Cullen","year":"2004","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"571816","DOI":"10.3389\/fimmu.2020.571816","article-title":"Phagocyte escape of Leptospira: The role of TLRs and NLRs","volume":"11","author":"Santecchia","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/j.1365-2958.2010.07360.x","article-title":"Mutations affecting Leptospira interrogans lipopolysaccharide attenuate virulence","volume":"78","author":"Murray","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1128\/IAI.01370-08","article-title":"Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans","volume":"77","author":"Murray","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ristow, P., Bourhy, P., da Cruz McBride, F.W., Figueira, C.P., Huerre, M., Ave, P., Girons, I.S., Ko, A.I., and Picardeau, M. (2007). The OmpA-like protein Loa22 is essential for leptospiral virulence. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030097"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1128\/IAI.00531-13","article-title":"Leptospiral outer membrane protein LipL41 is not essential for acute leptospirosis but requires a small chaperone protein, lep, for stable expression","volume":"81","author":"King","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1128\/IAI.01195-12","article-title":"Leptospiral LruA is required for virulence and modulates an interaction with mammalian apolipoprotein AI","volume":"81","author":"Zhang","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7888","DOI":"10.1128\/AEM.02202-15","article-title":"Control of gene expression in Leptospira spp. by transcription activator-like effectors demonstrates a potential role for LigA and LigB in Leptospira interrogans Virulence","volume":"81","author":"Pappas","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5826","DOI":"10.1128\/IAI.00989-08","article-title":"Targeted mutagenesis in pathogenic Leptospira species: Disruption of the LigB gene does not affect virulence in animal models of leptospirosis","volume":"76","author":"Croda","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ratet, G., Santecchia, I., Fanton d\u2019Andon, M., Vernel-Pauillac, F., Wheeler, R., Lenormand, P., Fischer, F., Lechat, P., Haake, D.A., and Picardeau, M. (2017). LipL21 lipoprotein binding to peptidoglycan enables Leptospira interrogans to escape NOD1 and NOD2 recognition. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006725"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1038\/nature01597","article-title":"Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing","volume":"422","author":"Ren","year":"2003","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.gene.2012.09.074","article-title":"Sequence of Leptospira santarosai serovar Shermani genome and prediction of virulence-associated genes","volume":"511","author":"Chou","year":"2012","journal-title":"Gene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1128\/jb.179.4.1262-1267.1997","article-title":"Identification and characterization of the dTDP-rhamnose biosynthesis and transfer genes of the lipopolysaccharide-related rfb locus in Leptospira interrogans serovar Copenhageni","volume":"179","author":"Mitchison","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_40","first-page":"103","article-title":"Ultrastructure and chemical composition of lipopolysaccharide extracted from Leptospira interrogans serovar Copenhageni","volume":"132","author":"Vinh","year":"1986","journal-title":"J. Gen. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1128\/JB.186.7.2164-2172.2004","article-title":"Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis","volume":"186","author":"Nascimento","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12335","DOI":"10.1074\/jbc.M112.418699","article-title":"Essential calcium-binding cluster of Leptospira LipL32 protein for inflammatory responses through the Toll-like receptor 2 pathway","volume":"288","author":"Lo","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.jmb.2009.05.034","article-title":"Structure and calcium-binding activity of LipL32, the major surface antigen of pathogenic Leptospira sp.","volume":"390","author":"Hauk","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.jmb.2009.02.038","article-title":"Crystal structure of LipL32, the most abundant surface protein of pathogenic Leptospira spp.","volume":"387","author":"Vivian","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1074\/jbc.M109.006320","article-title":"Calcium binds to LipL32, a lipoprotein from pathogenic Leptospira, and modulates fibronectin binding","volume":"285","author":"Tung","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1128\/IAI.01639-07","article-title":"In LipL32, the major leptospiral lipoprotein, the C terminus is the primary immunogenic domain and mediates interaction with collagen IV and plasma fibronectin","volume":"76","author":"Hauk","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1128\/IAI.01643-07","article-title":"LipL32 is an extracellular matrix-interacting protein of Leptospira spp. and Pseudoalteromonas tunicata","volume":"76","author":"Hoke","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/1574-6968.12349","article-title":"Leptospiral extracellular matrix adhesins as mediators of pathogen-host interactions","volume":"352","author":"Vieira","year":"2014","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.micpath.2010.05.006","article-title":"Effect of Leptospira interrogans outer membrane proteins LipL32 on HUVEC","volume":"49","author":"Sun","year":"2010","journal-title":"Microb. Pathog."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1681\/ASN.2006020159","article-title":"Leptospiral outer membrane protein induces extracellular matrix accumulation through a TGF-beta1\/Smad-dependent pathway","volume":"17","author":"Tian","year":"2006","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8363","DOI":"10.1038\/s41598-017-08743-y","article-title":"Active components of Leptospira outer membrane protein LipL32 to Toll-like receptor 2","volume":"7","author":"Hsu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1128\/IAI.71.5.2414-2421.2003","article-title":"LipL21 is a novel surface-exposed lipoprotein of pathogenic Leptospira species","volume":"71","author":"Cullen","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1128\/IAI.73.8.4853-4863.2005","article-title":"Surfaceome of Leptospira spp.","volume":"73","author":"Cullen","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"592858","DOI":"10.1155\/2014\/592858","article-title":"Production and characterization of a polyclonal antibody of anti-rLipL21-IgG against leptospira for early detection of acute leptospirosis","volume":"2014","author":"Seenichamy","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1080\/21505594.2021.1993427","article-title":"The leptospiral LipL21 and LipL41 proteins exhibit a broad spectrum of interactions with host cell components","volume":"12","author":"Mb","year":"2021","journal-title":"Virulence"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1080\/21505594.2017.1407484","article-title":"Leptospira interrogans outer membrane protein LipL21 is a potent inhibitor of neutrophil myeloperoxidase","volume":"9","author":"Vieira","year":"2018","journal-title":"Virulence"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.abb.2010.04.008","article-title":"Human myeloperoxidase in innate and acquired immunity","volume":"500","author":"Arnhold","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pinne, M., and Haake, D.A. (2009). A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006071"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Viratyosin, W., Ingsriswang, S., Pacharawongsakda, E., and Palittapongarnpim, P. (2008). Genome-wide subcellular localization of putative outer membrane and extracellular proteins in Leptospira interrogans serovar Lai genome using bioinformatics approaches. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-181"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s00284-010-9865-1","article-title":"Characterization of the immunogenic and antigenic potential of putative lipoproteins from Leptospira interrogans","volume":"62","author":"Hartwig","year":"2011","journal-title":"Curr. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0378-1097(03)00619-0","article-title":"Molecular cloning and characterization of a novel leptospiral lipoprotein with OmpA domain","volume":"226","author":"Koizumi","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s41598-020-79662-8","article-title":"Peptidoglycan mediates Leptospira outer membrane protein Loa22 to toll-like receptor 2 for inflammatory interaction: A novel innate immune recognition","volume":"11","author":"Hsu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1110\/ps.0303703","article-title":"Prediction of lipoprotein signal peptides in Gram-negative bacteria","volume":"12","author":"Juncker","year":"2003","journal-title":"Protein Sci. A Publ. Protein Soc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.bbrc.2005.03.097","article-title":"Escherichia coli outer membrane protein A adheres to human brain microvascular endothelial cells","volume":"330","author":"Shin","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1111\/j.1365-2958.1995.tb02348.x","article-title":"Proposal for a peptidoglycan-associating alpha-helical motif in the C-terminal regions of some bacterial cell-surface proteins","volume":"16","author":"Koebnik","year":"1995","journal-title":"Mol. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1111\/j.1365-2958.2003.03903.x","article-title":"Structure of the OmpA-like domain of RmpM from Neisseria meningitidis","volume":"51","author":"Grizot","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1128\/IAI.71.7.3937-3946.2003","article-title":"The C-terminal domain of Salmonella enterica serovar typhimurium OmpA is an immunodominant antigen in mice but appears to be only partially exposed on the bacterial cell surface","volume":"71","author":"Singh","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/2983","article-title":"Structure of the outer membrane protein A transmembrane domain","volume":"5","author":"Pautsch","year":"1998","journal-title":"Nat. Struct. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8008","DOI":"10.1128\/AEM.71.12.8008-8015.2005","article-title":"Differential binding of Escherichia coli O157:H7 to alfalfa, human epithelial cells, and plastic is mediated by a variety of surface structures","volume":"71","author":"Torres","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.immuni.2005.03.008","article-title":"Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors","volume":"22","author":"Jeannin","year":"2005","journal-title":"Immunity"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1128\/IAI.70.9.4936-4945.2002","article-title":"Characterization of the leptospiral outer membrane and description of three novel leptospiral membrane proteins","volume":"70","author":"Haake","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6356","DOI":"10.1128\/IAI.00460-06","article-title":"Newly identified leptospiral adhesin mediates attachment to laminin","volume":"74","author":"Barbosa","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Fouts, D.E., Matthias, M.A., Adhikarla, H., Adler, B., Amorim-Santos, L., Berg, D.E., Bulach, D., Buschiazzo, A., Chang, Y.F., and Galloway, R.L. (2016). What makes a bacterial species pathogenic?: Comparative genomic analysis of the genus Leptospira. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004403"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0959-440X(01)00266-4","article-title":"The leucine-rich repeat as a protein recognition motif","volume":"11","author":"Kobe","year":"2001","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1177\/1753425910377099","article-title":"The many faces of the YopM effector from plague causative bacterium Yersinia pestis and its implications for host immune modulation","volume":"17","author":"Soundararajan","year":"2011","journal-title":"Innate Immun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"18614","DOI":"10.1074\/jbc.M900581200","article-title":"Leucine-rich repeats of bacterial surface proteins serve as common pattern recognition motifs of human scavenger receptor gp340","volume":"284","author":"Loimaranta","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1128\/IAI.73.3.1671-1683.2005","article-title":"Characterization of a novel leucine-rich repeat protein antigen from group B streptococci that elicits protective immunity","volume":"73","author":"Seepersaud","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/S0092-8674(02)01136-4","article-title":"Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin","volume":"111","author":"Schubert","year":"2002","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"16360","DOI":"10.1074\/jbc.M110.100669","article-title":"The Salmonella type III secretion effector, salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3","volume":"285","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/S1097-2765(00)80234-8","article-title":"Structure of the lnlB leucine-rich repeats, a domain that triggers host cell invasion by the bacterial pathogen L. monocytogenes","volume":"4","author":"Marino","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ydbio.2005.05.045","article-title":"LrrA, a novel leucine-rich repeat protein involved in cytoskeleton remodeling, is required for multicellular morphogenesis in Dictyostelium discoideum","volume":"285","author":"Liu","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.1128\/IAI.72.8.4619-4627.2004","article-title":"Multiple functions of the leucine-rich repeat protein LrrA of Treponema denticola","volume":"72","author":"Ikegami","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1107\/S139900471500704X","article-title":"Structural characterization of a novel subfamily of leucine-rich repeat proteins from the human pathogen Leptospira interrogans","volume":"71","author":"Miras","year":"2015","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4161\/viru.25180","article-title":"Prediction of molecular mimicry candidates in human pathogenic bacteria","volume":"4","author":"Doxey","year":"2013","journal-title":"Virulence"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1007\/s00018-008-8019-0","article-title":"The leucine-rich repeat structure","volume":"65","author":"Bella","year":"2008","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_86","first-page":"46","article-title":"Identification of epitopes in Leptospira borgpetersenii leucine-rich repeat proteins","volume":"14","author":"Nitipan","year":"2013","journal-title":"Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1128\/jb.179.10.3188-3195.1997","article-title":"Molecular characterization and cellular localization of TpLRR, a processed leucine-rich repeat protein of Treponema pallidum, the syphilis spirochete","volume":"179","author":"Shevchenko","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5703","DOI":"10.1128\/IAI.66.12.5703-5710.1998","article-title":"Cloning, expression, and sequencing of a cell surface antigen containing a leucine-rich repeat motif from Bacteroides forsythus ATCC 43037","volume":"66","author":"Sharma","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1574-6968.1998.tb13087.x","article-title":"Molecular characterization of PcpA: A novel choline-binding protein of Streptococcus pneumoniae","volume":"164","author":"Lopez","year":"1998","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e82","DOI":"10.1038\/emi.2014.78","article-title":"Potential impact on kidney infection: A whole-genome analysis of Leptospira santarosai serovar Shermani","volume":"3","author":"Chou","year":"2014","journal-title":"Emerg Microbes Infect."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4313","DOI":"10.1042\/BCJ20200547","article-title":"Crystal structure of Leptospira leucine-rich repeat 20 reveals a novel E-cadherin binding protein to induce NGAL expression in HK2 cells","volume":"477","author":"Hsu","year":"2020","journal-title":"Biochem. J."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Hsu, S.H., Chou, L.F., Hong, C.H., Chang, M.Y., Tsai, C.Y., Tian, Y.C., Yang, H.Y., and Yang, C.W. (2021). Crosstalk between E-cadherin\/beta-catenin and NF-kappaB signaling pathways: The regulation of host-pathogen interaction during leptospirosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313132"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7259","DOI":"10.1128\/IAI.73.11.7259-7266.2005","article-title":"LruA and LruB, novel lipoproteins of pathogenic Leptospira interrogans associated with equine recurrent uveitis","volume":"73","author":"Verma","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Verma, A., Kumar, P., Babb, K., Timoney, J.F., and Stevenson, B. (2010). Cross-reactivity of antibodies against leptospiral recurrent uveitis-associated proteins A and B (LruA and LruB) with eye proteins. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000778"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1128\/IAI.74.3.1745-1750.2006","article-title":"Immunoprotection of recombinant leptospiral immunoglobulin-like protein A against Leptospira interrogans serovar Pomona infection","volume":"74","author":"Palaniappan","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1128\/IAI.01635-06","article-title":"Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen","volume":"75","author":"Choy","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.bbrc.2007.07.196","article-title":"A domain of the Leptospira LigB contributes to high affinity binding of fibronectin","volume":"362","author":"Lin","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Lin, M.H., Chang, Y.C., Hsiao, C.D., Huang, S.H., Wang, M.S., Ko, Y.C., Yang, C.W., and Sun, Y.J. (2013). LipL41, a hemin binding protein from Leptospira santarosai serovar Shermani. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083246"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.prevetmed.2010.05.017","article-title":"Spatial and spatio-temporal clustering of overall and serovar-specific Leptospira microscopic agglutination test (MAT) seropositivity among dogs in the United States from 2000 through 2007","volume":"96","author":"Gautam","year":"2010","journal-title":"Prev Vet Med"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1086\/346208","article-title":"Usefulness of serologic analysis as a predictor of the Infecting serovar in patients with severe leptospirosis","volume":"36","author":"Levett","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"695","DOI":"10.4269\/ajtmh.2009.09-0252","article-title":"The microscopic agglutination test (MAT) is an unreliable predictor of infecting Leptospira serovar in Thailand","volume":"81","author":"Smythe","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ijbiomac.2020.12.062","article-title":"Development of monoclonal antibodies against recombinant LipL21 protein of pathogenic Leptospira through phage display technology","volume":"168","author":"Sum","year":"2021","journal-title":"Int. J. Biol. Macromol"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3201\/eid1903.111260","article-title":"Human leptospirosis trends, The Netherlands, 1925\u20132008","volume":"19","author":"Goris","year":"2013","journal-title":"Emerg Infect. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcp.2018.03.001","article-title":"Development and validation of pan-Leptospira Taqman qPCR for the detection of Leptospira spp. in clinical specimens","volume":"38","author":"Ismail","year":"2018","journal-title":"Mol. Cell Probes"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.bjm.2017.09.004","article-title":"Development and validation of a modified TaqMan based real-time PCR assay targeting the lipl32 gene for detection of pathogenic Leptospira in canine urine samples","volume":"49","author":"Miotto","year":"2018","journal-title":"Braz. J. Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"9213","DOI":"10.1038\/s41598-018-27555-2","article-title":"Diagnosis of human leptospirosis in a clinical setting: Real-time PCR high resolution melting analysis for detection of Leptospira at the onset of disease","volume":"8","author":"Esteves","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cimid.2009.10.006","article-title":"Detection of Leptospira in urine using anti-Leptospira-coated gold nanoparticles","volume":"34","author":"Chirathaworn","year":"2011","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1128\/JCM.40.3.480-489.2002","article-title":"Diagnosis of human leptospirosis by monoclonal antibody-based antigen detection in urine","volume":"40","author":"Saengjaruk","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1089\/hyb.2006.033","article-title":"Monoclonal antibodies against LipL32, the major outer membrane protein of pathogenic Leptospira: Production, characterization, and testing in diagnostic applications","volume":"26","author":"Fernandes","year":"2007","journal-title":"Hybridoma"}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/12\/3\/300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:33:18Z","timestamp":1760135598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/12\/3\/300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,7]]},"references-count":109,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["membranes12030300"],"URL":"https:\/\/doi.org\/10.3390\/membranes12030300","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,7]]}}}