Leptospira as an emerging pathogen: A review of its biology, pathogenesis and host immune responses

Future Microbiology

Volumn 5, Issue 9, 2010, Pages 1413-1425

  Evangelista, Karen V ^a   Coburn, Jenifer ^a  

^a MEDICAL COLLEGE OF WISCONSIN   (United States)

Author keywords

epidemiology; leptospirosis; pathogenesis; virulence

Indexed keywords

INTERLEUKIN 6; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; VIRULENCE FACTOR;

BACTERIAL VIRULENCE; BACTERIUM IDENTIFICATION; CYTOLOGY; ENDEMIC DISEASE; GENETIC MANIPULATION; HUMAN; IMMUNE RESPONSE; IN VITRO STUDY; INCIDENCE; LEPTOSPIRA; LEPTOSPIRA ALEXANDERI; LEPTOSPIRA BIFLEXA; LEPTOSPIRA BORGPETERSENII; LEPTOSPIRA INTERROGANS; LEPTOSPIRA KIRSCHNERI; LEPTOSPIRA NOGUCHII; LEPTOSPIRA SANTAROSAI; LEPTOSPIRA WEILLI; LEPTOSPIROSIS; NONHUMAN; PATHOGENESIS; PATHOGENICITY; PRIORITY JOURNAL; REVIEW;

ACUTE DISEASE; ANIMALS; CHRONIC DISEASE; COMMUNICABLE DISEASES, EMERGING; CRICETINAE; DISEASE MODELS, ANIMAL; DOGS; GUINEA PIGS; HOST-PATHOGEN INTERACTIONS; HUMANS; LEPTOSPIRA; LEPTOSPIROSIS; MICE; RATS; VIRULENCE;

ANIMALIA; LEPTOSPIRA;

EID: 77957582069     PISSN: 17460913     EISSN: None     Source Type: Journal    
DOI: 10.2217/fmb.10.102     Document Type: Review

References (130)

1. Faine S, Adler B, Bolin C, Perolat P: Leptospira and Leptospirosis (Second Edition). Medisci, Melbourne, Australia (1999).
2. Benschop J, Heuer C, Jaros P, Collins-Emerson J, Midwinter A, Wilson P: Sero-prevalence of leptospirosis in workers at a New Zealand slaughterhouse. N. Z. Med. J. 122(1307), 39-47 (2009).
3. Desai S, Van Treeck U, Lierz M et al.: Resurgence of field fever in a temperate country: an epidemic of leptospirosis among seasonal strawberry harvesters in Germany in 2007. Clin. Infect. Dis. 48(6), 691-697 (2009).
4. CDC: Outbreak of acute febrile illness among athletes participating in triathlons - Wisconsin and Illinois, 1998. MMWR Morb. Mortal. Wkly Rep. 47(28), 585-588 (1998).
5. Morgan J, Bornstein S, Karpati A et al.: Outbreak of leptospirosis among triathlon participants and community residents in Springfield, Illinois, 1998. Clin. Infect. Dis. 34(12), 1593-1599 (2002).
6. Stern EJ, Galloway R, Shadomy SV et al.: Outbreak of leptospirosis among adventure race participants in Florida, 2005. Clin. Infect. Dis. 50(6), 843-849 (2010).
7. McBride A, Athanazio DA, Reis MG, Ko AI: Leptospirosis. Curr. Opin. Infect. Dis. 18(5), 376-386 (2005).
8. Kmety E, Dikken H: Classification of the Species Leptospira interrogans and History of its Serovars. University Press Gronigen, The Netherlands (1993).
9. Plank R, Dean D: Overview of the epidemiology, microbiology and pathogenesis of Leptospira spp. in humans. Microbes Infect. 2(10), 1265-1276 (2000).
10. Adler B, Moctezuma A: Leptospira and leptospirosis. Vet. Microbiol. 140(3-4), 287-296 (2010).
11. Bharti AR, Nally JE, Ricaldi JN et al.: Leptospirosis: a zoonotic disease of global importance. Lancet Infect. Dis. 3(12), 757-771 (2003).
12. Brenner DJ, Kaufmann AF, Sulzer KR, Steigerwalt AG, Rogers FC, Weyant RS: Further determination of DNA relatedness between serogroups and serovars in the family Leptospiraceae with a proposal for Leptospira alexanderi sp. nov. and four new Leptospira genomospecies. Int. J. Syst. Bacteriol. 49(2), 839-858 (1999).
13. Levett P: Leptospirosis. Clin. Microbiol. Rev. 14(2), 296-326 (2001).
14. Ahmed N, Devi SM, Valverde Mde L et al.: Multilocus sequence typing method for identification and genotypic classification of pathogenic Leptospira species. Ann. Clin. Microbiol. Antimicrob. 5, 28 (2006).
15. Palaniappan R, Ramanujam S, Chang Y: Leptospirosis: pathogenesis, immunity, and diagnosis. Curr. Opin. Infect. Dis. 20(3), 284-292 (2007).
16. Levett PN, Morey RE, Galloway RL, Steigerwalt AG: Leptospira broomii sp. nov., isolated from humans with leptospirosis. Int. J. Syst. Evol. Microbiol. 56(Pt 3), 671-673 (2006).
17. Perolat P, Chappel RJ, Adler B et alLeptospira fainei sp. nov., isolated from pigs in Australia. Int. J. Syst. Bacteriol. 48(Pt 3), 851-858 (1998).
18. Haake DA: Spirochaetal lipoproteins and pathogenesis. Microbiology 146(7), 1491-1504 (2000).
19. Ko A, Goarant C, Piccardeau M: Leptospira: the dawn of molecular genetics era for an emerging zoonotic pathogen. Nat. Rev. Microbiol. 7, 736-746 (2009).
20. Vijayachari P, Sugunan AP, Shriram AN: Leptospirosis: an emerging global public health problem. J. Biosci. 33(4), 557-569 (2008).
21. Charon NW, Goldstein SF: Genetics of motility and chemotaxis of a fascinating group of bacteria: the spirochetes. Annu. Rev. Genet. 36, 47-73 (2002).
22. Picardeau M, Brenot A, Saint Girons I: First evidence for gene replacement in Leptospira spp. inactivation of L. biflexa flaB results in non-motile mutants deficient in endoflagella. Mol. Microbiol. 40(1), 189-199 (2001).
23. Wolgemuth CW, Charon NW, Goldstein SF, Goldstein RE: The flagellar cytoskeleton of the spirochetes. J. Mol. Microbiol. Biotechnol. 11(3-5), 221-227 (2006).
24. Liao S, Sun A, Ojcius DM, Wu S, Zhao J, Yan J: Inactivation of the fliY gene encoding a flagellar motor switch protein attenuates mobility and virulence of Leptospira interrogans strain Lai. BMC Microbiol. 9, 253 (2009).
25. Murray P, Rosenthal K, Pfaller M: Medical Microbiology (6th Edition). Mosby Elsevier, PA, USA (2009).
26. Trueba G, Zapata S, Madrid K, Cullen P, Haake D: Cell aggregation: a mechanism of pathogenic Leptospira to survive in fresh water. Int. Microbiol. 7(1), 35-40 (2004).
27. Bulach DM, Zuerner RL, Wilson P et alGenome reduction in Leptospira borgpetersenii reflects limited transmission potential. Proc. Natl Acad. Sci. 103(39), 14560-14565 (2006).
28. Ristow P, Bourhy P, Kerneis S et alBiofilm formation by saprophytic and pathogenic leptospires. Microbiology 154(Pt 5), 1309-1317 (2008).
29. Pappas G, Papadimitriou P, Siozopoulou V, Christou L, Akritidis N: The globalization of leptospirosis: worldwide incidence trends. Int. J. Infect. Dis. 12(4), 351-357 (2008).
30. Victoriano A, Smythe L, Gloriani-Barzaga N et alLeptospirosis in the Asia Pacific region. BMC Infect. Dis. 9, 147 (2009).
31. Sejvar J, Bancroft E, Winthrop K et alLeptospirosis in Eco-challenge Athletes, Malaysian Borneo, 2000. Emerg. Infect. Dis. 9(6), 702-707 (2003).
32. Teichmann D, Göbels K, Simon J, Grobusch MP, Suttorp N: A severe case of leptospirosis acquired during an iron man contest. Eur. J. Clin. Microbiol. Infect. Dis. 20(2), 137-138 (2001).
33. Ciceroni L, Stepan E, Pinto A et alEpidemiological trend of human leptospirosis in Italy between 1994 and 1996. Eur. J. Epidemiol. 16(1), 79-86 (2000).
34. McCurry J: Philippines struggles to recover from typhoons. Lancet 347(9700), 1489 (2009).
35. Ko AI, Galvâ̂o Reis M, Ribeiro Dourado CM, Johnson WDJ, Riley LW: Urban epidemic of severe leptospirosis in Brazil. Lancet 354(9181), 820-825 (1999).
36. Kariv R, Klempfner R, Barnea A, Sidi Y, Schwartz E: The changing epidemiology of leptospirosis in Israel. Emerg. Infect. Dis. 7(6), 990-992 (2001).
37. Nascimento A, Ko AI, Martins EAL et alComparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis. J. Bacteriol. 186(7), 2164-2172 (2004).
38. Picardeau M, Bulach D, Bouchier C et alGenome sequence of the saprophyte Leptospira biflexa provides insights into the evolution of Leptospira and the pathogenesis of leptospirosis. PLoS One 3(2), e1607 (2008).
39. Ren SX, Fu G, Jiang XG et alUnique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing. Nature 422(6934), 888-893 (2003).
40. Haake DA: Hamster model of leptospirosis. Curr. Protoc. Microbiol. Chapter 12, Unit12E.2 (2006).
41. Griffith ME, Hospenthal DR, Murray CK: Antimicrobial therapy of leptospirosis. Curr. Opin. Infect. Dis. 19(6), 533-537 (2006).
42. Nally JE, Chantranuwat C, Wu XY et alAlveolar septal deposition of immunoglobulin and complement parallels pulmonary hemorrhage in a guinea pig model of severe pulmonary leptospirosis. Am. J. Pathol. 164(3), 1115-1127 (2004).
43. Silva EF, Medeiros MA, McBride AJ et alThe terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis. Vaccine 25(33), 6277-6286 (2007).
44. Silva EF, Santos CS, Athanazio DA et alCharacterization of virulence of Leptospira isolates in a hamster model. Vaccine 29(31), 3892-3896 (2008).
45. Vernel-Pauillac F, Goarant C: Differential cytokine gene expression according to outcome in a hamster model of leptospirosis. PLoS Negl. Trop. Dis. 4(1), e582 (2010).
46. Truccolo J, Charavay F, Merien F, Perolat P: Quantitative PCR assay to evaluate ampicillin, ofloxacin, and doxycycline for treatment of experimental leptospirosis. Antimicrob. Agents Chemother. 46(3), 848-853 (2002).
47. Bolin CA, Alt DP: Use of a monovalent leptospiral vaccine to prevent renal colonization and urinary shedding in cattle exposed to Leptospira borgpetersenii serovar Hardjo. Am. J. Vet. Res. Microbiol. 62(7), 995-1000 (2001).
48. Athanazio DA, Silva EF, Santos CS et alRattus norvegicus as a model for persistent renal colonization by pathogenic Leptospira interrogans. Acta Trop. 105(2), 176-180 (2008)
49. Palaniappan R, McDonough S, Divers T et alImmunoprotection of recombinant leptospiral immunoglobulin-like protein A against Leptospira interrogans serovar Pomona infection. Infect. Immun. 74(3), 1745-1750 (2006).
50. Koizumi N, Watanabe H: Leptospiral immunoglobulin-like proteins elicit protective immunity. Vaccine 22(11-12), 1545-1552 (2004).
51. Adler B, Faine S: Host immunological mechanisms in the resistance of mice to leptospiral infections. Infect. Immun. 17(1), 67-72 (1977).
52. Gibbs RA, Weinstock GM, Metzker ML et alGenome sequence of the brown Norway rat yields insights into mammalian evolution. Nature 428(6982), 493-521 (2004).
53. Tucunduva De Faria MT, Athanazio DA, Gonalves Ramos EA, Silva EF, Reis MG, Ko AI: Morphological alterations in the kidney of rats with natural and experimental Leptospira infection. J. Comp. Pathol. 137(4), 231-238 (2007).
54. Nally JE, Fishbein MC, Blanco DR, Lovett MA: Lethal infection of C3H/HEJ and C3H/SCID mice with an isolate of Leptospira interrogans serovar Copenhageni. Infect. Immun. 73(10), 7014-7017 (2005).
55. Pereira MM, Andrade J, Marchevsky RS, Ribeiro Dos Santos R: Morphological characterization of lung and kidney lesions in C3H/HEJ mice infected with Leptospira interrogans serovar Icterohaemorrhagiae: defect of CD4+ and CD8+ T-cells are prognosticators of the disease progression. Exp. Toxicol. Pathol. 50(3), 191-198 (1998).
56. Neely MN, Pfeifer JD, Caparon M: Streptococcus-zebrafish model of bacterial pathogenesis. Infect. Immun. 70(7), 3904-3914 (2002).
57. Swaim LE, Connolly LE, Volkman HE, Humbert O, Born DE, Ramakrishnan L: Mycobacterium marinum infection of adult zebrafish causes caseating granulomatous tuberculosis and is moderated by adaptive immunity. Infect. Immun. 74(11), 6108-6117 (2006).
58. Davis JM, Haake DA, Ramakrishnan L: Leptospira interrogans stably infects zebrafish embryos, altering phagocyte behavior and homing to specific tissues. PLoS Negl. Trop. Dis. 3(6), e463 (2009).
59. Faine S: Virulence in Leptospira. II. The growth in vivo of virulent Leptospira icterohaemorrhagiae. Br. J. Exp. Pathol. 38(1), 8-14 (1957).
60. Pereira MM, Da Silva J, Pinto MA et alExperimental leptospirosis in marmoset monkeys (Callithrix jacchus): a new model for studies of severe pulmonary leptospirosis. Am. J. Trop. Med. Hyg. 72(1), 13-20 (2005).
61. Saint Girons I, Margarita D, Amouriaux P, Baranton G: First isolation of bacteriophages for a spirochaete: potential genetic tools for Leptospira. Res. Microbiol. 141(9), 1131-1138 (1990).
62. Saint Girons I, Bourhy P, Ottone C et alThe LE1 bacteriophage replicates as a plasmid within Leptospira biflexa: construction of an L. biflexa-Escherichia coli shuttle vector J. Bacteriol. 183(20), 5700-5705 (2000).
63. Picardeau M: Conjugative transfer between Escherichia coli and Leptospira spp. as a new genetic tool. Appl. Environ. Microb. 74(1), 319-322 (2008).
64. Tchamedeu Kameni AP, Couture-Tosi E, Saint-Girons I, Picardeau M: Inactivation of the spirochete recA gene results in a mutant with low viability and irregular nucleoid morphology. J. Bacteriol. 184(2), 452-458 (2002).
65. Bauby H, Saint Girons I, Picardeau M: Construction and complementation of the first auxotrophic mutant in the spirochaete Leptospira meyeri. Microbiology 149, 689-693 (2003).
66. Guégan R, Camadro JM, Saint Girons I, Picardeau M: Leptospira spp. possess a complete haem biosynthetic pathway and are able to use exogenous haem sources. Mol. Microbiol. 49(3), 745-754 (2003).
67. Louvel H, Picardeau M: Genetic manipulation of Leptospira biflexa. Curr. Protoc. Microbiol. Chapter 12, Unit 12E.4 (2007).
68. Croda J, Figueira C, Wunder E et alTargeted mutagenesis in pathogenic Leptospira species: Disruption of the ligB gene does not affect virulence in animal models of leptospirosis. Infect. Immun. 76(12), 5826-5833 (2008).
69. Murray GL, Srikram A, Hoke DE et alMajor surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans. Infect. Immun. 77(3), 952-958 (2009).
70. Bourhy P, Louvel H, Saint Girons I, Picardeau M: Random insertional mutagenesis of Leptospira interrogans, the agent of leptospirosis, using a mariner transposon. J. Bacteriol. 187(9), 3255-3258 (2005).
71. Murray GL, Morel V, Cerqueira GM et alGenome-wide transposon mutagenesis in pathogenic Leptospira species. Infect. Immun. 77(2), 810-816 (2009).
72. Louvel H, Saint Girons I, Picardeau M: Isolation and characterization of FecA- and FeoB-mediated iron acquisition systems of the spirochete Leptospira biflexa by random insertional mutagenesis. J. Bacteriol. 187(9), 3249-3254 (2005).
73. Ristow P, Bourhy P, Mcbride F et alThe OmpA-like protein Loa22 is essential for leptospiral virulence. PLoS Pathog. 3(7), e97 (2007).
74. Ter Huurne AA, Muir SS, Van Houten M, Van Der Zeijst BA, Gaastra W, Kusters JG: Characterization of three putative Serpulina hyodysenteriae hemolysins. Microb. Pathog. 16(4), 269-282 (1994).
75. Carvalho E, Barbosa AS, Gòmez RM et alLeptospiral TlyC is an extracellular matrix-binding protein and does not present hemolysin activity. FEBS Lett. 583(8), 1381-1385 (2009).
76. Berheimer AW, Bey RF: Copurification of Leptospira interrogans serovar Pomona hemolysin and sphingomyelinase C. Infect. Immun. 54(1), 262-264 (1986).
77. Segers R, Van Gestel JA, Van Eys G, Van Der Zeijst B, Gaastra B: Presence of putative sphingomyelinase genes among members of the family Leptospiraceae. Infect. Immun. 60(4), 1707-1710 (1992).
78. Lee SH, Kim S, Park SC, Kim MJ: Cytotoxic activities of Leptospira interrogans hemolysin SphH as a pore-forming protein on mammalian cells. Infect. Immun. 70(1), 315-322 (2002).
79. Lee SH, Kim KA, Park YG, Seong IW, Kim MJ, Lee YJ: Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar Lai. Gene 254(1-2), 19-28 (2000).
80. Artiushin S, Timoney JF, Nally J, Verma A: Host-inducible immunogenic sphingomyelinase-like protein, Lk73.5, of Leptospira interrogans. Infect. Immun. 72(2), 742-749 (2004).
81. Carvalho E, Barbosa AS, Gomez RM et alEvaluation of the expression and protective potential of leptospiral sphingomyelinases. Curr. Microbiol. 60(2), 134-142 (2010).
82. Zhang Y, Geng Y, Yang J, Guo X, Zhao G: Cytotoxic activity and probable apoptotic effect of Sph2, a sphigomyelinase hemolysin from Leptospira interrogans strain Lai. BMB Rep. 41(2), 119-125 (2008).
83. Patti JM, Allen BL, McGavin MJ, Höök M: MSCRAMM-mediated adherence of microorganisms to host tissues. Annu. Rev. Microbiol. 48, 585-617 (1994).
84. Schwarz-Linek U, Höök M, Potts JR: The molecular basis of fibronectin-mediated bacterial adherence to host cells. Mol. Microbiol. 52(3), 631-641 (2004).
85. Breiner D, Fahey M, Salvador R, Novakova J, Coburn J: Leptospira interrogans binds to human cell surface receptors including proteoglycans. Infect. Immun. 77(12), 5528-5536 (2009).
86. Pinne M, Haake DA: A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans. PLoS One 4(6), E6071 (2009).
87. Matsunaga J, Barocchi MA, Croda C et alPathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily. Mol. Microbiol. 49(4), 929-949 (2003).
88. Palaniappan R, Chang Y, Jusuf S et alCloning and molecular characterization of an immunogenic LigA protein of Leptospira interrogans. Infect. Immun. 70(11), 5924-5930 (2002).
89. Luo Y, Frey EA, Pfuetzner RA et alCrystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature 405(6790), 1073-1077 (2000).
90. Hamburger ZA, Brown MS, Isberg RR, Bjorkman PJ: Crystal structure of invasin: a bacterial integrin-binding protein. Science 286(5438), 291-295 (1999).
91. Choy HA, Kelley MM, Chen TL, Møller AK, Matsunaga J, Haake DA: Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen. Infect. Immun. 75(5), 2241-2450 (2007).
92. Lin Y, Greenwood A, Yan W et alA novel fibronectin type III module binding motif identified on C-terminus of Leptospira immunoglobulin-like protein, LigB. Biochem. Biophys. Res. Commun. 389(1), 57-62 (2009).
93. Lin YP, Lee D, McDonough SP, Nicholson LK, Sharma Y, Chang YF: Repeated domains of Leptospira immunoglobulin-like proteins interact with elastin and tropoelastin. J. Biol. Chem. 284(29), 19380-19391 (2009).
94. Lin YP, Raman R, Sharma Y, Chang YF: Calcium binds to leptospiral immunoglobulin-like protein, LigB, and modulates fibronectin binding. J. Biol. Chem. 283(37), 25140-25149 (2008).
95. Lin YP, Chang YF: A domain of the Leptospira LigB contributes to high affinity binding of fibronectin. Biochem. Biophys. Res. Commun. 362(2), 443-448 (2007).
96. Lin YP, Chang YF: The C-terminal variable domain of LigB from Leptospira mediates binding to fibronectin. J. Vet. Sci. 9(2), 133-144 (2008).
97. Barbosa AS, Abreu P, Neves FO et alA newly identified leptospiral adhesin mediates attachment to laminin. Infect. Immun. 74(11), 6356-6364 (2006).
98. Stevenson B, Choy HA, Pinne M et alLeptospira interrogans endostatin-like outer membrane proteins bind host fibronectin, laminin and regulators of complement. PLoS One 2(11), e1188 (2007).
99. Verma A, Brissette CA, Bowman AA, Shah ST, Zipfel PF, Stevenson B: Leptospiral endostatin-like protein a is a bacterial cell surface receptor for human plasminogen. Infect. Immun. 78(5), 2053-2059 (2010).
100. Verma A, Hellwage J, Artiushin S et alLfhA, a novel factor H-binding protein of Leptospira interrogans. Infect. Immun. 74(5), 2659-2666 (2006).
101. Atzingen MV, Barbosa AS, De Brito T et alLsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection. BMC Microbiol. 8, 70 (2008).
102. Longhi MT, Oliveira TR, Romero EC et alA newly identified protein of Leptospira interrogans mediates binding to laminin. J. Med. Microbiol. 58(Pt 10), 1275-1282 (2009).
103. Vieira ML, De Morais ZM, Goncales AP, Romero EC, Vasconcellos SA, Nascimento AL: Lsa63, a newly identified surface protein of Leptospira interrogans binds laminin and collagen IV. J. Infect. 60(1), 52-64 (2010).
104. Merien F, Truccolo J, Baranton G, Perolat P: Identification of a 36-kDa fibronectin-binding protein expressed by a virulent variant of Leptospira interrogans serovar Icterohaemorrhagiae. FEMS Microbiol. Lett. 185(1), 17-22 (2000).
105. Haake DA, Chao G, Zuerner RL et alThe leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect. Immun. 68(4), 2276-2285 (2000).
106. Hauk P, Macedo F, Romero EC et alIn LipL32, the major leptospiral lipoprotein, the C-terminus is the primary immunogenic domain and mediates interaction with collagen IV and plasma fibronectin. Infect. Immun. 76(6), 2642-2650 (2008).
107. Hoke DE, Egan S, Cullen PA, Adler B: LipL32 is an extracellular matrix-interacting protein of Leptospira spp. and Pseudoalteromonas tunicata. Infect. Immun. 76(5), 2063-2069 (2008).
108. Tung J, Yang C, Chou S, Lin C, Sun Y: Calcium binds to LipL32, a lipoprotein from pathogenic Leptospira, and modulates fibronectin binding. J. Biol. Chem. 285(5), 3245-3252 (2010).
109. Koizumi N, Watanabe H: Molecular cloning and characterization of a novel leptospiral lipoprotein with OmpA domain. FEMS Microbiol. Lett. 226(2), 215-219 (2003).
110. Nally JE, Whitelegge JP, Bassilian S, Blanco DR, Lovett MA: Characterization of the outer membrane proteome of Leptospira interrogans expressed during acute lethal infection. Infect. Immun. 75(2), 766-773 (2007).
111. Gamberini M, Gòmez RM, Atzingen MV et alWhole-genome analysis of Leptospira interrogans to identify potential vaccine candidates against leptospirosis. FEMS Microbiol. Lett. 244(2), 305-313 (2005).
112. Lo M, Bulach DM, Powell DR et alEffects of temperature on gene expression patterns in Leptospira interrogans serovar Lai as assessed by whole-genome microarrays. Infect. Immun. 74(10), 5848-5859 (2006).
113. Lo M, Cordwell SJ, Bulach DM, Adler B: Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature. PLoS Negl. Trop. Dis. 3(12), e560 (2009).
114. Matsunaga J, Lo M, Bulach DM, Zuerner RL, Adler B, Haake DA: Response of Leptospira interrogans to physiologic osmolarity: relevance in signaling the environment-to-host transition. Infect. Immun. 75(6), 2864-2874 (2007).
115. Qin JH, Sheng YY, Zhang ZM et alGenome-wide transcriptional analysis of temperature shift in L. interrogans serovar Lai strain 56601. BMC Microbiol. 6, 51 (2006).
116. Matsunaga J, Sanchez Y, Xu X, Haake DA: Osmolarity, a key environmental signal controlling expression of leptospiral proteins LigA and LigB and the extracellular release of LigA. Infect. Immun. 73(1), 70-78 (2005).
117. Nally JE, Artiushin S, Timoney JF: Molecular characterization of thermoinduced immunogenic proteins Qlp42 and Hsp15 of Leptospira interrogans. Infect. Immun. 69(12), 7616-7624 (2001)
118. Jost BH, Adler B, Vinh T, Faine S: A monoclonal antibody reacting with a determinant on leptospiral lipopolysaccharide protects guinea pigs against leptospirosis. J. Med. Microbiol. 22(3), 269-275 (1986).
119. Cumberland P, Everard COR, Wheeler JG, Levett PN: Persistence of anti-leptospiral IgM, IgG and agglutinating antibodies in patients presenting with acute febrile illness in Barbados 1979-1989. Eur. J. Epidemiol. 17(7), 601-608 (2001).
120. Haake DA, Mazel MK, McCoy AM et alLeptospiral outer membrane proteins OmpL1 and LipL41 exhibit synergistic immunoprotection. Infect. Immun. 67(12), 6572-6582 (1999).
121. Yan W, Faisal SM, McDonough SP et alImmunogenicity and protective efficacy of recombinant Leptospira immunoglobulin-like protein B (rLigB) in a hamster challenge model. Microbes Infect. 11(2), 230-237 (2009).
122. Chassin C, Picardeau M, Goujon JM et alTLR4- and TLR2-mediated B cell responses control the clearance of the bacterial pathogen, Leptospira interrogans. J. Immunol. 183(4), 2669-2677 (2009).
123. Nahori M, Fournié-Amazouz E, Que-Gewirth NS et alDifferential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells. J. Immunol. 175(9), 6022-6031 (2005).
124. Viriyakosol S, Matthias MA, Swancutt MA, Kirkland TN, Vinetz JM: Toll-like receptor 4 protects against lethal Leptospira interrogans serovar Icterohaemorrhagiae infection and contributes to in vivo control of leptospiral burden. Infect. Immun. 74(2), 887-895 (2006).
125. Werts C, Tapping RI, Mathison JC et alLeptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat. Immunol. 2(4), 346-352 (2001).
126. Vinh T, Adler B, Faine S: The role of macrophages in the protection of mice against leptospirosis: in vitro and in vivo studies. Pathology 14(4), 463-468 (1982).
127. Li S, Ojcius DM, Liao S et alReplication or death: distinct fates of pathogenic Leptospira strain Lai within macrophages of human or mouse origin. Innate Immun. 16(2), 80-92 (2010).
128. Eshghi A, Cullen PA, Cowen L, Zuerner RL, Cameron CE: Global proteome analysis of Leptospira interrogans. J. Proteome Res. 8(10), 4564-4578 (2009).
129. Monahan AM, Callanan JJ, Nally JE: Proteomic analysis of Leptospira interrogans shed in urine of chronically infected hosts. Infect. Immun. 76(11), 4952-4958 (2008).
130. Malmstrom J, Beck M, Schmidt A, Lange V, Deutsch EW, Aebersold R: Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans. Nature 460(7256), 762-765 (2009)