Leptospira as an Emerging Pathogen: A Review of its Biology, Pathogenesis and Host Immune Responses

Bibliography

• Faine S , AdlerB, BolinC, PerolatP: Leptospira and Leptospirosis (Second Edition). Medisci, Melbourne, Australia (1999).
   Google Scholar
• Benschop J , HeuerC, JarosP, Collins-EmersonJ, MidwinterA, WilsonP: Sero-prevalence of leptospirosis in workers at a New Zealand slaughterhouse.N. Z. Med. J.122(1307) , 39–47 (2009).
   PubMedGoogle Scholar
• Desai S , Van TreeckU, LierzMet 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).
   PubMed Web of Science ®Google Scholar
• 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).
   PubMedGoogle Scholar
• Morgan J , BornsteinS, KarpatiAet al. : Outbreak of leptospirosis among triathlon participants and community residents in Springfield, Illinois, 1998.Clin. Infect. Dis.34(12) , 1593–1599 (2002).
   PubMed Web of Science ®Google Scholar
• Stern EJ , GallowayR, ShadomySVet al. : Outbreak of leptospirosis among adventure race participants in Florida, 2005.Clin. Infect. Dis.50(6) , 843–849 (2010).
   PubMed Web of Science ®Google Scholar
• McBride A , AthanazioDA, ReisMG, KoAI: Leptospirosis.Curr. Opin. Infect. Dis.18(5) , 376–386 (2005).
   PubMed Web of Science ®Google Scholar
• Kmety E , DikkenH: Classification of the Species Leptospira interrogans and History of its Serovars.University Press Gronigen,The Netherlands (1993).
   Google Scholar
• Plank R , DeanD: Overview of the epidemiology, microbiology and pathogenesis of Leptospira spp. in humans.Microbes Infect.2(10) , 1265–1276 (2000).
   PubMed Web of Science ®Google Scholar
• Adler B , MoctezumaA: Leptospira and leptospirosis.Vet. Microbiol.140(3–4) , 287–296 (2010).
   PubMed Web of Science ®Google Scholar
• Bharti AR , NallyJE, RicaldiJNet al. : Leptospirosis: a zoonotic disease of global importance.Lancet Infect. Dis.3(12) , 757–771 (2003).
   PubMed Web of Science ®Google Scholar
• Brenner DJ , KaufmannAF, SulzerKR, SteigerwaltAG, RogersFC, WeyantRS: 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).
   PubMedGoogle Scholar
• Levett P : Leptospirosis.Clin. Microbiol. Rev.14(2) , 296–326 (2001).
   PubMed Web of Science ®Google Scholar
• Ahmed N , DeviSM, ValverdeMde Let al.: Multilocus sequence typing method for identification and genotypic classification of pathogenic Leptospira species. Ann. Clin. Microbiol. Antimicrob.5 , 28 (2006).
   PubMedGoogle Scholar
• Palaniappan R , RamanujamS, ChangY: Leptospirosis: pathogenesis, immunity, and diagnosis.Curr. Opin. Infect. Dis.20(3) , 284–292 (2007).
   PubMed Web of Science ®Google Scholar
• Levett PN , MoreyRE, GallowayRL, SteigerwaltAG: Leptospira broomii sp. nov., isolated from humans with leptospirosis.Int. J. Syst. Evol. Microbiol.56(Pt 3) , 671–673 (2006).
   PubMed Web of Science ®Google Scholar
• Perolat P , ChappelRJ, AdlerBet al. : Leptospira fainei sp. nov., isolated from pigs in Australia.Int. J. Syst. Bacteriol.48(Pt 3) , 851–858 (1998).
   PubMedGoogle Scholar
• Haake DA : Spirochaetal lipoproteins and pathogenesis.Microbiology146(7) , 1491–1504 (2000).
   PubMedGoogle Scholar
• Ko A , GoarantC, PiccardeauM: Leptospira: the dawn of molecular genetics era for an emerging zoonotic pathogen.Nat. Rev. Microbiol.7 , 736–746 (2009).
   PubMed Web of Science ®Google Scholar
• Vijayachari P , SugunanAP, ShriramAN: Leptospirosis: an emerging global public health problem.J. Biosci.33(4) , 557–569 (2008).
   PubMed Web of Science ®Google Scholar
• Charon NW , GoldsteinSF: Genetics of motility and chemotaxis of a fascinating group of bacteria: the spirochetes.Annu. Rev. Genet.36 , 47–73 (2002).
   PubMed Web of Science ®Google Scholar
• Picardeau M , BrenotA, Saint GironsI: 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).
   PubMed Web of Science ®Google Scholar
• Wolgemuth CW , CharonNW, GoldsteinSF, GoldsteinRE: The flagellar cytoskeleton of the spirochetes.J. Mol. Microbiol. Biotechnol.11(3–5) , 221–227 (2006).
   PubMed Web of Science ®Google Scholar
• Liao S , SunA, OjciusDM, WuS, ZhaoJ, YanJ: 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).
   PubMed Web of Science ®Google Scholar
• Murray P , RosenthalK, PfallerM: Medical Microbiology (6th Edition).Mosby Elsevier,PA, USA (2009).
   Google Scholar
• Trueba G , ZapataS, MadridK, CullenP, HaakeD: Cell aggregation: a mechanism of pathogenic Leptospira to survive in fresh water.Int. Microbiol.7(1) , 35–40 (2004).
   PubMed Web of Science ®Google Scholar
• Bulach DM , ZuernerRL, WilsonPet al. : Genome reduction in Leptospira borgpetersenii reflects limited transmission potential.Proc.Natl Acad. Sci.103(39) , 14560–14565 (2006).
   PubMed Web of Science ®Google Scholar
• Ristow P , BourhyP, KerneisSet al. : Biofilm formation by saprophytic and pathogenic leptospires.Microbiology154(Pt 5) , 1309–1317 (2008).
   PubMed Web of Science ®Google Scholar
• Pappas G , PapadimitriouP, SiozopoulouV, ChristouL, AkritidisN: The globalization of leptospirosis: worldwide incidence trends.Int. J. Infect. Dis.12(4) , 351–357 (2008).
   PubMed Web of Science ®Google Scholar
• Victoriano A , SmytheL, Gloriani-BarzagaNet al. : Leptospirosis in the Asia Pacific region.BMC Infect. Dis.9 , 147 (2009).
   PubMed Web of Science ®Google Scholar
• Sejvar J , BancroftE, WinthropKet al. : Leptospirosis in “Eco-challenge” Athletes, Malaysian Borneo, 2000.Emerg. Infect. Dis.9(6) , 702–707 (2003).
   PubMed Web of Science ®Google Scholar
• Teichmann D , GöbelsK, SimonJ, GrobuschMP, SuttorpN: A severe case of leptospirosis acquired during an iron man contest.Eur. J. Clin. Microbiol. Infect. Dis.20(2) , 137–138 (2001).
   PubMed Web of Science ®Google Scholar
• Ciceroni L , StepanE, PintoAet al. : Epidemiological trend of human leptospirosis in Italy between 1994 and 1996.Eur. J. Epidemiol.16(1) , 79–86 (2000).
   PubMed Web of Science ®Google Scholar
• McCurry J : Philippines struggles to recover from typhoons.Lancet347(9700) , 1489 (2009).
   Google Scholar
• Ko AI , GalvãoReis M, RibeiroDourado CM, JohnsonWDJ, RileyLW: Urban epidemic of severe leptospirosis in Brazil.Lancet354(9181) , 820–825 (1999).
   PubMed Web of Science ®Google Scholar
• Kariv R , KlempfnerR, BarneaA, SidiY, SchwartzE: The changing epidemiology of leptospirosis in Israel.Emerg. Infect. Dis.7(6) , 990–992 (2001).
   PubMed Web of Science ®Google Scholar
• Nascimento A , KoAI, MartinsEALet al. : Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis.J. Bacteriol.186(7) , 2164–2172 (2004).
   PubMed Web of Science ®Google Scholar
• Picardeau M , BulachD, BouchierCet al. : Genome sequence of the saprophyte Leptospira biflexa provides insights into the evolution of Leptospira and the pathogenesis of leptospirosis.PLoS One3(2) , e1607 (2008).
   PubMed Web of Science ®Google Scholar
• Ren SX , FuG, JiangXGet al. : Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing.Nature422(6934) , 888–893 (2003).
   PubMed Web of Science ®Google Scholar
• Haake DA : Hamster model of leptospirosis.Curr. Protoc. Microbiol. Chapter 12, Unit12E.2 (2006).
   PubMedGoogle Scholar
• Griffith ME , HospenthalDR, MurrayCK: Antimicrobial therapy of leptospirosis.Curr. Opin. Infect. Dis.19(6) , 533–537 (2006).
   PubMed Web of Science ®Google Scholar
• Nally JE , ChantranuwatC, WuXYet al. : Alveolar 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).
   PubMed Web of Science ®Google Scholar
• Silva EF , MedeirosMA, McBrideAJet al. : The terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis.Vaccine25(33) , 6277–6286 (2007).
   PubMed Web of Science ®Google Scholar
• Silva EF , SantosCS, AthanazioDAet al. : Characterization of virulence of Leptospira isolates in a hamster model.Vaccine29(31) , 3892–3896 (2008).
   Google Scholar
• Vernel-Pauillac F , GoarantC: Differential cytokine gene expression according to outcome in a hamster model of leptospirosis.PLoS Negl. Trop. Dis.4(1) , e582 (2010).
   PubMed Web of Science ®Google Scholar
• Truccolo J , CharavayF, MerienF, PerolatP: Quantitative PCR assay to evaluate ampicillin, ofloxacin, and doxycycline for treatment of experimental leptospirosis.Antimicrob. Agents Chemother.46(3) , 848–853 (2002).
   PubMed Web of Science ®Google Scholar
• Bolin CA , AltDP: 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).
   PubMed Web of Science ®Google Scholar
• Athanazio DA , SilvaEF, SantosCSet al. : Rattus norvegicus as a model for persistent renal colonization by pathogenic Leptospira interrogans.Acta Trop.105(2) , 176–180 (2008).
   PubMed Web of Science ®Google Scholar
• Palaniappan R , McDonoughS, DiversTet al. : Immunoprotection of recombinant leptospiral immunoglobulin-like protein A against Leptospira interrogans serovar Pomona infection.Infect. Immun.74(3) , 1745–1750 (2006).
   PubMed Web of Science ®Google Scholar
• Koizumi N , WatanabeH: Leptospiral immunoglobulin-like proteins elicit protective immunity.Vaccine22(11–12) , 1545–1552 (2004).
   PubMed Web of Science ®Google Scholar
• Adler B , FaineS: Host immunological mechanisms in the resistance of mice to leptospiral infections.Infect. Immun.17(1) , 67–72 (1977).
   PubMed Web of Science ®Google Scholar
• Gibbs RA , WeinstockGM, MetzkerMLet al. : Genome sequence of the brown Norway rat yields insights into mammalian evolution.Nature428(6982) , 493–521 (2004).
   PubMed Web of Science ®Google Scholar
• Tucunduva De Faria MT , AthanazioDA, GonçalvesRamos EA, SilvaEF, ReisMG, KoAI: Morphological alterations in the kidney of rats with natural and experimental Leptospira infection.J. Comp. Pathol.137(4) , 231–238 (2007).
   PubMed Web of Science ®Google Scholar
• Nally JE , FishbeinMC, BlancoDR, LovettMA: Lethal infection of C3H/HEJ and C3H/SCID mice with an isolate of Leptospira interrogans serovar Copenhageni.Infect. Immun.73(10) , 7014–7017 (2005).
   PubMed Web of Science ®Google Scholar
• Pereira MM , AndradeJ, MarchevskyRS, Ribeiro DosSantos 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).
   PubMedGoogle Scholar
• Neely MN , PfeiferJD, CaparonM: Streptococcus –zebrafish model of bacterial pathogenesis.Infect. Immun.70(7) , 3904–3914 (2002).
   PubMed Web of Science ®Google Scholar
• Swaim LE , ConnollyLE, VolkmanHE, HumbertO, BornDE, RamakrishnanL: Mycobacterium marinum infection of adult zebrafish causes caseating granulomatous tuberculosis and is moderated by adaptive immunity.Infect. Immun.74(11) , 6108–6117 (2006).
   PubMed Web of Science ®Google Scholar
• Davis JM , HaakeDA, RamakrishnanL: Leptospira interrogans stably infects zebrafish embryos, altering phagocyte behavior and homing to specific tissues.PLoS Negl. Trop. Dis.3(6) , e463 (2009).
   PubMed Web of Science ®Google Scholar
• Faine S : Virulence in Leptospira. II. The growth in vivo of virulent Leptospira icterohaemorrhagiae.Br. J. Exp. Pathol.38(1) , 8–14 (1957).
   PubMedGoogle Scholar
• Pereira MM , Da SilvaJ, PintoMAet al. : Experimental 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).
   PubMed Web of Science ®Google Scholar
• Saint Girons I , MargaritaD, AmouriauxP, BarantonG: First isolation of bacteriophages for a spirochaete: potential genetic tools for Leptospira.Res. Microbiol.141(9) , 1131–1138 (1990).
   PubMed Web of Science ®Google Scholar
• Saint Girons I , BourhyP, OttoneCet al. : The 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).
   Google Scholar
• Picardeau M : Conjugative transfer between Escherichia coli and Leptospira spp. as a new genetic tool.Appl. Environ. Microb.74(1) , 319–322 (2008).
   PubMed Web of Science ®Google Scholar
• Tchamedeu Kameni AP , Couture-TosiE, Saint-GironsI, PicardeauM: Inactivation of the spirochete recA gene results in a mutant with low viability and irregular nucleoid morphology.J. Bacteriol.184(2) , 452–458 (2002).
   PubMed Web of Science ®Google Scholar
• Bauby H , SaintGirons I, PicardeauM: Construction and complementation of the first auxotrophic mutant in the spirochaete Leptospira meyeri.Microbiology149 , 689–693 (2003).
   PubMed Web of Science ®Google Scholar
• Guégan R , CamadroJM, SaintGirons I, PicardeauM: Leptospira spp. possess a complete haem biosynthetic pathway and are able to use exogenous haem sources.Mol. Microbiol.49(3) , 745–754 (2003).
   PubMed Web of Science ®Google Scholar
• Louvel H , PicardeauM: Genetic manipulation of Leptospira biflexa.Curr. Protoc. Microbiol. Chapter 12, Unit 12E.4 (2007).
   PubMedGoogle Scholar
• Croda J , FigueiraC, WunderEet al. : Targeted 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).
   PubMed Web of Science ®Google Scholar
• Murray GL , SrikramA, HokeDEet al. : Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans.Infect. Immun.77(3) , 952–958 (2009).
   PubMed Web of Science ®Google Scholar
• Bourhy P , LouvelH, SaintGirons I, PicardeauM: Random insertional mutagenesis of Leptospira interrogans, the agent of leptospirosis, using a mariner transposon.J. Bacteriol.187(9) , 3255–3258 (2005).
   PubMed Web of Science ®Google Scholar
• Murray GL , MorelV, CerqueiraGMet al. : Genome-wide transposon mutagenesis in pathogenic Leptospira species.Infect. Immun.77(2) , 810–816 (2009).
   PubMed Web of Science ®Google Scholar
• Louvel H , SaintGirons I, PicardeauM: 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).
   PubMed Web of Science ®Google Scholar
• Ristow P , BourhyP, McbrideFet al. : The OmpA-like protein Loa22 is essential for leptospiral virulence.PLoS Pathog.3(7) , e97 (2007).
   PubMed Web of Science ®Google Scholar
• Ter Huurne AA , MuirSS, Van HoutenM, Van DerZeijst BA, GaastraW, KustersJG: Characterization of three putative Serpulina hyodysenteriae hemolysins.Microb. Pathog.16(4) , 269–282 (1994).
   PubMed Web of Science ®Google Scholar
• Carvalho E , BarbosaAS, GómezRMet al. : Leptospiral TlyC is an extracellular matrix-binding protein and does not present hemolysin activity.FEBS Lett.583(8) , 1381–1385 (2009).
   PubMed Web of Science ®Google Scholar
• Berheimer AW , BeyRF: Copurification of Leptospira interrogans serovar Pomona hemolysin and sphingomyelinase C.Infect. Immun.54(1) , 262–264 (1986).
   PubMed Web of Science ®Google Scholar
• Segers R , Van GestelJA, Van EysG, Van DerZeijst B, GaastraB: Presence of putative sphingomyelinase genes among members of the family Leptospiraceae.Infect. Immun.60(4) , 1707–1710 (1992).
   PubMed Web of Science ®Google Scholar
• Lee SH , KimS, ParkSC, KimMJ: Cytotoxic activities of Leptospira interrogans hemolysin SphH as a pore-forming protein on mammalian cells.Infect. Immun.70(1) , 315–322 (2002).
   PubMed Web of Science ®Google Scholar
• Lee SH , KimKA, ParkYG, SeongIW, KimMJ, LeeYJ: Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar Lai.Gene254(1–2) , 19–28 (2000).
   PubMed Web of Science ®Google Scholar
• Artiushin S , TimoneyJF, NallyJ, VermaA: Host-inducible immunogenic sphingomyelinase-like protein, Lk73.5, of Leptospira interrogans.Infect. Immun.72(2) , 742–749 (2004).
   PubMed Web of Science ®Google Scholar
• Carvalho E , BarbosaAS, GomezRMet al. : Evaluation of the expression and protective potential of leptospiral sphingomyelinases.Curr. Microbiol.60(2) , 134–142 (2010).
   PubMed Web of Science ®Google Scholar
• Zhang Y , GengY, YangJ, GuoX, ZhaoG: Cytotoxic activity and probable apoptotic effect of Sph2, a sphigomyelinase hemolysin from Leptospira interrogans strain Lai.BMB Rep.41(2) , 119–125 (2008).
   PubMed Web of Science ®Google Scholar
• Patti JM , AllenBL, McGavinMJ, HöökM: MSCRAMM-mediated adherence of microorganisms to host tissues.Annu. Rev. Microbiol.48 , 585–617 (1994).
   PubMed Web of Science ®Google Scholar
• Schwarz-Linek U , HöökM, PottsJR: The molecular basis of fibronectin-mediated bacterial adherence to host cells.Mol. Microbiol.52(3) , 631–641 (2004).
   PubMed Web of Science ®Google Scholar
• Breiner D , FaheyM, SalvadorR, NovakovaJ, CoburnJ: Leptospira interrogans binds to human cell surface receptors including proteoglycans.Infect. Immun.77(12) , 5528–5536 (2009).
   PubMed Web of Science ®Google Scholar
• Pinne M , HaakeDA: A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans.PLoS One4(6) , E6071 (2009).
   PubMed Web of Science ®Google Scholar
• Matsunaga J , BarocchiMA, CrodaCet al. : Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily.Mol. Microbiol.49(4) , 929–949 (2003).
   PubMed Web of Science ®Google Scholar
• Palaniappan R , ChangY, JusufSet al. : Cloning and molecular characterization of an immunogenic LigA protein of Leptospira interrogans.Infect. Immun.70(11) , 5924–5930 (2002).
   PubMed Web of Science ®Google Scholar
• Luo Y , FreyEA, PfuetznerRAet al. : Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex.Nature405(6790) , 1073–1077 (2000).
   PubMed Web of Science ®Google Scholar
• Hamburger ZA , BrownMS, IsbergRR, BjorkmanPJ: Crystal structure of invasin: a bacterial integrin-binding protein.Science286(5438) , 291–295 (1999).
   PubMed Web of Science ®Google Scholar
• Choy HA , KelleyMM, ChenTL, M⊘llerAK, MatsunagaJ, HaakeDA: Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen.Infect. Immun.75(5) , 2241–2450 (2007).
   Web of Science ®Google Scholar
• Lin Y , GreenwoodA, YanWet al. : A 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).
   PubMed Web of Science ®Google Scholar
• Lin YP , LeeD, McDonoughSP, NicholsonLK, SharmaY, ChangYF: Repeated domains of Leptospira immunoglobulin-like proteins interact with elastin and tropoelastin.J. Biol. Chem.284(29) , 19380–19391 (2009).
   PubMed Web of Science ®Google Scholar
• Lin YP , RamanR, SharmaY, ChangYF: Calcium binds to leptospiral immunoglobulin-like protein, LigB, and modulates fibronectin binding.J. Biol. Chem.283(37) , 25140–25149 (2008).
   PubMed Web of Science ®Google Scholar
• Lin YP , ChangYF: A domain of the Leptospira LigB contributes to high affinity binding of fibronectin.Biochem. Biophys. Res. Commun.362(2) , 443–448 (2007).
   PubMed Web of Science ®Google Scholar
• Lin YP , ChangYF: The C-terminal variable domain of LigB from Leptospira mediates binding to fibronectin.J. Vet. Sci.9(2) , 133–144 (2008).
   PubMed Web of Science ®Google Scholar
• Barbosa AS , AbreuP, NevesFOet al. : A newly identified leptospiral adhesin mediates attachment to laminin.Infect. Immun.74(11) , 6356–6364 (2006).
   PubMed Web of Science ®Google Scholar
• Stevenson B , ChoyHA, PinneMet al. : Leptospira interrogans endostatin-like outer membrane proteins bind host fibronectin, laminin and regulators of complement.PLoS One2(11) , e1188 (2007).
   PubMed Web of Science ®Google Scholar
• Verma A , BrissetteCA, BowmanAA, ShahST, ZipfelPF, StevensonB: Leptospiral endostatin-like protein a is a bacterial cell surface receptor for human plasminogen.Infect. Immun.78(5) , 2053–2059 (2010).
   PubMed Web of Science ®Google Scholar
• Verma A , HellwageJ, ArtiushinSet al. : LfhA, a novel factor H-binding protein of Leptospira interrogans.Infect. Immun.74(5) , 2659–2666 (2006).
   PubMed Web of Science ®Google Scholar
• Atzingen MV , BarbosaAS, De BritoTet al.: Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection.BMC Microbiol.8 , 70 (2008).
   PubMed Web of Science ®Google Scholar
• Longhi MT , OliveiraTR, RomeroECet al. : A newly identified protein of Leptospira interrogans mediates binding to laminin.J. Med. Microbiol.58(Pt 10) , 1275–1282 (2009).
   PubMed Web of Science ®Google Scholar
• Vieira ML , De MoraisZM, GoncalesAP, RomeroEC, VasconcellosSA, NascimentoAL: Lsa63, a newly identified surface protein of Leptospira interrogans binds laminin and collagen IV.J. Infect.60(1) , 52–64 (2010).
   PubMed Web of Science ®Google Scholar
• Merien F , TruccoloJ, BarantonG, PerolatP: 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).
   PubMed Web of Science ®Google Scholar
• Haake DA , ChaoG, ZuernerRLet al. : The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection.Infect. Immun.68(4) , 2276–2285 (2000).
   PubMed Web of Science ®Google Scholar
• Hauk P , MacedoF, RomeroECet al. : In 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).
   PubMed Web of Science ®Google Scholar
• Hoke DE , EganS, CullenPA, AdlerB: LipL32 is an extracellular matrix-interacting protein of Leptospira spp. and Pseudoalteromonas tunicata.Infect. Immun.76(5) , 2063–2069 (2008).
   PubMed Web of Science ®Google Scholar
• Tung J , YangC, ChouS, LinC, SunY: Calcium binds to LipL32, a lipoprotein from pathogenic Leptospira, and modulates fibronectin binding.J. Biol. Chem.285(5) , 3245–3252 (2010).
   PubMed Web of Science ®Google Scholar
• Koizumi N , WatanabeH: Molecular cloning and characterization of a novel leptospiral lipoprotein with OmpA domain.FEMS Microbiol. Lett.226(2) , 215–219 (2003).
   PubMed Web of Science ®Google Scholar
• Nally JE , WhiteleggeJP, BassilianS, BlancoDR, LovettMA: Characterization of the outer membrane proteome of Leptospira interrogans expressed during acute lethal infection.Infect. Immun.75(2) , 766–773 (2007).
   PubMed Web of Science ®Google Scholar
• Gamberini M , GómezRM, AtzingenMVet al. : Whole-genome analysis of Leptospira interrogans to identify potential vaccine candidates against leptospirosis.FEMS Microbiol. Lett.244(2) , 305–313 (2005).
   PubMed Web of Science ®Google Scholar
• Lo M , BulachDM, PowellDRet al. : Effects of temperature on gene expression patterns in Leptospira interrogans serovar Lai as assessed by whole-genome microarrays.Infect. Immun.74(10) , 5848–5859 (2006).
   PubMed Web of Science ®Google Scholar
• Lo M , CordwellSJ, BulachDM, AdlerB: Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature.PLoS Negl. Trop. Dis.3(12) , e560 (2009).
   PubMed Web of Science ®Google Scholar
• Matsunaga J , LoM, BulachDM, ZuernerRL, AdlerB, HaakeDA: Response of Leptospira interrogans to physiologic osmolarity: relevance in signaling the environment-to-host transition.Infect. Immun.75(6) , 2864–2874 (2007).
   PubMed Web of Science ®Google Scholar
• Qin JH , ShengYY, ZhangZMet al. : Genome-wide transcriptional analysis of temperature shift in L. interrogans serovar Lai strain 56601.BMC Microbiol.6 , 51 (2006).
   PubMed Web of Science ®Google Scholar
• Matsunaga J , SanchezY, XuX, HaakeDA: 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).
   PubMed Web of Science ®Google Scholar
• Nally JE , ArtiushinS, TimoneyJF: Molecular characterization of thermoinduced immunogenic proteins Qlp42 and Hsp15 of Leptospira interrogans.Infect. Immun.69(12) , 7616–7624 (2001).
   PubMed Web of Science ®Google Scholar
• Jost BH , AdlerB, VinhT, FaineS: A monoclonal antibody reacting with a determinant on leptospiral lipopolysaccharide protects guinea pigs against leptospirosis.J. Med. Microbiol.22(3) , 269–275 (1986).
   PubMed Web of Science ®Google Scholar
• Cumberland P , EverardCOR, WheelerJG, LevettPN: 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).
   PubMed Web of Science ®Google Scholar
• Haake DA , MazelMK, McCoyAMet al. : Leptospiral outer membrane proteins OmpL1 and LipL41 exhibit synergistic immunoprotection.Infect. Immun.67(12) , 6572–6582 (1999).
   PubMed Web of Science ®Google Scholar
• Yan W , FaisalSM, McDonoughSPet al. : Immunogenicity and protective efficacy of recombinant Leptospira immunoglobulin-like protein B (rLigB) in a hamster challenge model.Microbes Infect.11(2) , 230–237 (2009).
   PubMed Web of Science ®Google Scholar
• Chassin C , PicardeauM, GoujonJMet al. : TLR4- and TLR2-mediated B cell responses control the clearance of the bacterial pathogen, Leptospira interrogans.J. Immunol.183(4) , 2669–2677 (2009).
   PubMed Web of Science ®Google Scholar
• Nahori M , Fournié-AmazouzE, Que-GewirthNSet al. : Differential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells.J. Immunol.175(9) , 6022–6031 (2005).
   PubMed Web of Science ®Google Scholar
• Viriyakosol S , MatthiasMA, SwancuttMA, KirklandTN, VinetzJM: 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).
   PubMed Web of Science ®Google Scholar
• Werts C , TappingRI, MathisonJCet al. : Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism.Nat. Immunol.2(4) , 346–352 (2001).
   PubMed Web of Science ®Google Scholar
• Vinh T , AdlerB, FaineS: The role of macrophages in the protection of mice against leptospirosis: in vitro and in vivo studies.Pathology14(4) , 463–468 (1982).
   PubMed Web of Science ®Google Scholar
• Li S , OjciusDM, LiaoSet al. : Replication or death: distinct fates of pathogenic Leptospira strain Lai within macrophages of human or mouse origin.Innate Immun.16(2) , 80–92 (2010).
   PubMed Web of Science ®Google Scholar
• Eshghi A , CullenPA, CowenL, ZuernerRL, CameronCE: Global proteome analysis of Leptospira interrogans.J. Proteome Res.8(10) , 4564–4578 (2009).
   PubMed Web of Science ®Google Scholar
• Monahan AM , CallananJJ, NallyJE: Proteomic analysis of Leptospira interrogans shed in urine of chronically infected hosts.Infect. Immun.76(11) , 4952–4958 (2008).
   PubMed Web of Science ®Google Scholar
• Malmstrom J , BeckM, SchmidtA, LangeV, DeutschEW, AebersoldR: Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans.Nature460(7256) , 762–765 (2009).
   PubMed Web of Science ®Google Scholar