Genomics, Proteomics, and Genetics of Leptospira

  • Mathieu Picardeau
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 387)


Recent advances in molecular genetics, such as the ability to construct defined mutants, have allowed the study of virulence factors and more generally the biology in Leptospira. However, pathogenic leptospires remain much less easily transformable than the saprophyte L. biflexa and further development and improvement of genetic tools are required. Here, we review tools that have been used to genetically manipulate Leptospira. We also describe the major advances achieved in both genomics and postgenomics technologies, including transcriptomics and proteomics.


Genomic Island Pathogenic Leptospira Leptospira Species Saprophytic Strain Amino Acid Biosynthesis Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Original work in the author’s laboratory was supported by Institut Pasteur and Agence Nationale de la Recherche (05-JCJC-0105 and 08-MIE-018).


  1. Adler B, Lo M, Seemann T, Murray GL (2011) Pathogenesis of leptospirosis: the influence of genomics. Vet Microbiol 153:73–81PubMedCrossRefGoogle Scholar
  2. Aviat F, Slamti L, Cerqueira GM, Lourdault KMP (2010) Expanding the genetic toolbox for Leptospira species by generation of fluorescent bacteria. Appl Environ Microbiol 76:8135–8142PubMedCentralPubMedCrossRefGoogle Scholar
  3. Ballard SA, Segers RP, Bleumink-Pluym N, Fyfe J, Faine S, Adler B (1993) Molecular analysis of the hsp (groE) operon of Leptospira interrogans serovar copenhageni. Mol Microbiol 8:739–751PubMedCrossRefGoogle Scholar
  4. Baril C, Herrmann JL, Richaud C, Margarita D, Girons IS (1992a) Scattering of the rRNA genes on the physical map of the circular chromosome of Leptospira interrogans serovar icterohaemorrhagiae. J Bacteriol 174:7566–7571PubMedCentralPubMedGoogle Scholar
  5. Baril C, Richaud C, Fournie E, Baranton G, Saint Girons I (1992b) Cloning of dapD, aroD and asd of Leptospira interrogans serovar icterohaemorrhagiae, and nucleotide sequence of the asd gene. J Gen Microbiol 138:47–53PubMedCrossRefGoogle Scholar
  6. Bauby H, Saint Girons I, Picardeau M (2003) Construction and complementation of the first auxotrophic mutant in the spirochaete Leptospira meyeri. Microbiology 149:689–693PubMedCrossRefGoogle Scholar
  7. Beck M, Malmström JA, Lange V, Schmidt A, Deutsch EW, Aebersold R (2009) Visual proteomics of the human pathogen Leptospira interrogans. Nat Methods 6:817–823PubMedCentralPubMedCrossRefGoogle Scholar
  8. Belfaiza J, Martel A, Margarita D, Saint Girons I (1998) Direct sulfhydrylation for methionine biosynthesis in Leptospira meyeri. J Bacteriol 180:250–255PubMedCentralPubMedGoogle Scholar
  9. Bourhy P, Saint Girons I (2000) Localization of the Leptospira interrogans metF gene on the CII secondary chromosome. FEMS Microbiol Lett 191:259–263PubMedCrossRefGoogle Scholar
  10. Bourhy P, Frangeul L, Couve E, Glaser P, Saint Girons I, Picardeau M (2005a) Complete nucleotide sequence of the LE1 prophage from the spirochete Leptospira biflexa and characterization of its replication and partition functions. J Bacteriol 187:3931–3940PubMedCentralPubMedCrossRefGoogle Scholar
  11. Bourhy P, Louvel H, Saint Girons I, Picardeau M (2005b) Random insertional mutagenesis of Leptospira interrogans, the agent of leptospirosis, using a mariner transposon. J Bacteriol 187:3255–3258PubMedCentralPubMedCrossRefGoogle Scholar
  12. Bourhy P, Salaün L, Lajus A, Médigue C, Boursaux-Eude C, Picardeau M (2007) A genomic island of the pathogen Leptospira interrogans serovar Lai can excise from its chromosome. Infect Immun 75:677–683PubMedCentralPubMedCrossRefGoogle Scholar
  13. Boursaux-Eude C, Saint Girons I, Zuerner RL (1995) IS1500, an IS3-like element from Leptospira interrogans. Microbiology 141:2165–2173PubMedCrossRefGoogle Scholar
  14. Bulach DM, Zuerner RL, Wilson P, Seemann T, McGrath A, Cullen PA, Davis J, Johnson M, Kuczek E, Alt DP, Peterson-Burch B, Coppel RL, Rood JI, Davies JK, Adler B (2006) Genome reduction in Leptospira borgpetersenii reflects limited transmission potential. Proc Natl Acad Sci USA 103:14560–14565PubMedCentralPubMedCrossRefGoogle Scholar
  15. Caimano MJ, Sivasankaran SK, Allard A, Hurley D, Hokamp K, Grassmann AA, Hinton JC, Nally JE (2014) A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni. PLoS Pathog 13,10(3):e1004004Google Scholar
  16. Cao XJ, Dai J, Xu H, Nie S, Chang X, Hu BY, Sheng QH, Wang LS, Ning ZB, Li YX, Guo XK, Zhao GP, Zeng R (2010) High-coverage proteome analysis reveals the first insight of protein modification systems in the pathogenic spirochete Leptospira interrogans. Cell Res 20:197–210PubMedCrossRefGoogle Scholar
  17. Cerqueira GM, Picardeau M (2009) A century of Leptospira strain typing. Infect Genet Evol 9:760–768PubMedCrossRefGoogle Scholar
  18. Cerqueira GM, Souza NM, Araújo ER, Barros AT, Morais ZM, Vasconcellos SA, Nascimento AL (2011) Development of transcriptional fusions to assess Leptospira interrogans promoter activity. PLoS ONE 6:e17409PubMedCentralPubMedCrossRefGoogle Scholar
  19. Chou LF, Chen YT, Lu CW, Ko YC, Tang CY, Pan MJ, Tian YC, Chiu CH, Hung CC, Yang CW (2012) Sequence of Leptospira santarosai serovar Shermani genome and prediction of virulence-associated genes. Gene 11:364–370CrossRefGoogle Scholar
  20. Croda J, Figueira CP, Wunder EAJ, Santos CS, Reis MG, Ko AI, Picardeau M (2008) Targeted mutagenesis in pathogenic Leptospira: disruption of the ligB gene does not affect virulence in animal models of leptospirosis. Infect Immun 76:5826–5833PubMedCentralPubMedCrossRefGoogle Scholar
  21. Cullen PA, Cordwell SJ, Bulach DM, Haake DA, Adler B (2002) Global analysis of outer membrane proteins from Leptospira interrogans serovar Lai. Infect Immun 70:2311–2318PubMedCentralPubMedCrossRefGoogle Scholar
  22. Cuñé J, Cullen P, Mazon G, Campoy S, Adler B, Barbe J (2005) The Leptospira interrogans lexA gene is not autoregulated. J Bacteriol 187:5841–5845PubMedCentralPubMedCrossRefGoogle Scholar
  23. DelaPeña-Moctezuma A, Bulach DM, Kalambaheti T, Adler B (2001) Genetic differences among the LPS biosynthetic loci of serovars of Leptospira interrogans and Leptospira borgpetersenii. FEMS Immunol Med 31:73–81CrossRefGoogle Scholar
  24. Eshghi A, Cullen PA, Cowen L, Zuerner RL, Cameron CE (2009) Global proteome analysis of Leptospira interrogans. J Proteome Res 8:4564–4578PubMedCentralPubMedCrossRefGoogle Scholar
  25. Eshghi A, Lourdault K, Murray GL, Bartpho T, Sermswan RW, Picardeau M, Adler B, Snarr B, Zuerner RL, Cameron CE (2012a) Leptospira interrogans catalase is required for resistance to H2O2 and for virulence. Infect Imm 80(11):3892-3899Google Scholar
  26. Eshghi A, Pinne M, Haake DA, Zuerner RL, Frank A, Cameron CE (2012b) Methylation and in vivo expression of the surface-exposed Leptospira interrogans outer-membrane protein OmpL32. Microbiology 158:622–635PubMedCentralPubMedCrossRefGoogle Scholar
  27. Falkow S (1988) Molecular Koch’s postulates applied to microbial pathogenicity. Rev Infect Dis 10:274–276CrossRefGoogle Scholar
  28. Figueira CP, Croda J, Choy HA, Haake DA, Reis MG, Ko AI, Picardeau M (2011) Heterologous expression of pathogen-specific genes ligA and ligB in the saprophyte Leptospira biflexa confers enhanced adhesion to cultured cells and fibronectin. BMC Microbiol 11:129PubMedCentralPubMedCrossRefGoogle Scholar
  29. Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, White O, Ketchum KA, Dodson R, Hickey EK, Gwinn M, Dougherty B, Tomb JF, Fleischmann RD, Richardson D, Peterson J, Kerlavage AR, Quackenbush J, Salzberg S, Hanson M, Vanvugt R, Palmer N, Adams MD, Gocayne J, Weidman J et al (1997) Genomic sequence of a lyme disease spirochaete, Borrelia burgdorferi. Nature 390:580–586PubMedCrossRefGoogle Scholar
  30. Fraser CM, Norris SJ, Weinstock CM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Fujii C et al (1998) Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281:375–388PubMedCrossRefGoogle Scholar
  31. Fukunaga M, Horie I, Mifuchi I (1989) Nucleotide sequence of a 23S ribosomal RNA gene from Leptospira interrogans serovar canicola strain Moulton. Nucleic Acids Res 17:2123PubMedCentralPubMedCrossRefGoogle Scholar
  32. Haake DA, Martinich C, Summers TA, Shang ES, Pruetz JD, McCoy AM, Mazel MK, Bolin CA (1998) Characterization of Leptospiral outer membrane lipoprotein LipL36: downregulation associated with late-log-phase growth and mammalian infection. Infect Immun 66:1579–1587PubMedCentralPubMedGoogle Scholar
  33. Haake DA, Matsunaga J (2010) Leptospira: a spirochaete with a hybrid outer membrane. Mol Microbiol 77:805-814Google Scholar
  34. Hardham JM, Rosey EL (2000) Antibiotic selective markers and spirochete genetics. J Mol Microbiol Biotechnol 2:425–432PubMedGoogle Scholar
  35. Harrison PW, Lower RP, Kim NK, Young JP (2010) Introducing the bacterial chromid: not a chromosome, not a plasmid. Trends Microbiol 18:141–148PubMedCrossRefGoogle Scholar
  36. He P, Sheng YY, Shi YZ, Jiang XG, Qin JH, Zhang ZM, Zhao GP, Guo XK (2007) Genetic diversity among major endemic strains of Leptospira interrogans in China. BMC Genom 8:204CrossRefGoogle Scholar
  37. Henry R, Lo M, Khoo C, Zhang H, Boysen RI, Picardeau M, Murray GL, Bulach DM, Adler B (2013) Iron precipitation on the surface of Leptospira interrogans is associated with mutation of the stress-response metalloprotease HtpX. Appl Environ Microbiol 79:4653–4660Google Scholar
  38. Kassegne K, Hu W, Ojcius DM, Sun D, Ge Y, Zhao J, Yang XF, Li L, Yan J (2014) Identification of collagenase as a critical virulence factor for invasiveness and transmission of pathogenic Leptospira species. J Infect Dis 209:1105–1115PubMedCrossRefGoogle Scholar
  39. King AM, Bartpho T, Sermswan RW, Bulach DM, Eshghi A, Picardeau M, Adler B, Murray GL (2013) Leptospiral outer membrane protein LipL41 is not essential for acute leptospirosis, but requires a small chaperone, Lep, for stable expression. Infect Immun 81:2768–2776PubMedCentralPubMedCrossRefGoogle Scholar
  40. King AM, Pretre G, Bartpho T, Sermswan RW, Toma C, Suzuki T, Eshghi A, Picardeau M, Adler B, Murray GL (2014) High temperature protein G (HtpG) is an essential virulence factor of Leptospira interrogans. Infect Immun 82:1123–1131PubMedCentralPubMedCrossRefGoogle Scholar
  41. Ko AI, Galvao Reis M, Ribeiro Dourado CM, Johnson WD Jr, Riley LW (1999) Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group Lancet 354:820–825Google Scholar
  42. Lambert A, Picardeau M, Haake DA, Sermswan RW, Srikram A, Adler B, Murray GA (2012) FlaA proteins in Leptospira interrogans are essential for motility and virulence but are not required for formation of the flagellum sheath. Infect Immun 80:2019–2025PubMedCentralPubMedCrossRefGoogle Scholar
  43. Liao S, Sun A, Ojcius DM, Wu S, Zhao J, Yan J (2009) Inactivation of the fliY gene encoding a flagellar motor switch protein attenuates mobility and virulence of Leptospira interrogans strain Lai. BMC Microbiol 9:253PubMedCentralPubMedCrossRefGoogle Scholar
  44. Lo M, Bulach DM, Powell DR, Haake DA, Matsunaga J, Paustian ML, Zuerner RL, Adler B (2006) Effects of temperature on gene expression patterns in Leptospira interrogans serovar Lai as assessed by whole-genome microarrays. Infect Immun 74:848–859CrossRefGoogle Scholar
  45. Lo M, Cordwell SJ, Bulach DM, Adler B (2009) Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature. PLoS Negl Trop Dis 3:560CrossRefGoogle Scholar
  46. Lo M, Murray GL, Khoo CA, Haake DA, Zuerner RL, Adler B (2010) Transcriptional response of Leptospira interrogans to iron limitation and characterization of a PerR homolog. Infect Immun 78:4850–4859PubMedCentralPubMedCrossRefGoogle Scholar
  47. Lourdault K, Cerqueira GM, Wunder EAMP (2011) Inactivation of clpB in the pathogen Leptospira interrogans reduces virulence and resistance to stress conditions. Infect Immun 79:3711–3717PubMedCentralPubMedCrossRefGoogle Scholar
  48. Louvel H, Saint Girons I, Picardeau M (2005) Isolation and characterization of FecA- and FeoB- mediated iron acquisition systems of the spirochete Leptospira biflexa by random insertional mutagenesis. J Bacteriol 187:3249–3254PubMedCentralPubMedCrossRefGoogle Scholar
  49. Louvel H, Bommezzadri S, Zidane N, Boursaux-Eude C, Creno S, Magnier A, Rouy Z, Medigue C, Girons IS, Bouchier C, Picardeau M (2006) Comparative and functional genomic analyses of iron transport and regulation in Leptospira spp. J Bacteriol 188:7893–7904PubMedCentralPubMedCrossRefGoogle Scholar
  50. Louvel H, Picardeau M (2007) Genetic manipulation of Leptospira biflexa. Wiley, HobokenGoogle Scholar
  51. Louvel H, Betton JM, Picardeau M (2008) Heme rescues a two-component system Leptospira biflexa mutant. BMC Microbiol 8:25PubMedCentralPubMedCrossRefGoogle Scholar
  52. Malmström J, Beck M, Schmidt A, Lange V, Deutsch EW, Aebersold R (2009) Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans. Nature 460:762–765PubMedCentralPubMedCrossRefGoogle Scholar
  53. Matsui M, Soupé ME, Becam J, Goarant C (2012) Differential in vivo gene expression of major Leptospira proteins in resistant or susceptible animal models. Appl Environ Microbiol 78:6372–6376PubMedCentralPubMedCrossRefGoogle Scholar
  54. Matsunaga J, Sanchez Y, Xu X, Haake DA (2005) Osmolarity, a key environmental signal controlling expression of Leptospiral proteins LigA and LigB and the extracellular release of LigA. Infect Immun 73:70–78PubMedCentralPubMedCrossRefGoogle Scholar
  55. Matsunaga J, Schlax PJ, Haake DA (2013) Role for cis-acting RNA sequences in the temperature-dependent expression of the multiadhesive lig proteins in Leptospira interrogans. J Bacteriol 195:5092–5101PubMedCentralPubMedCrossRefGoogle Scholar
  56. Matsunaga J, Lo M, Bulach DM, Zuerner RL, Adler B, Haake DA (2007) Response of Leptospira interrogans to physiologic osmolarity: relevance in signaling the environment-to-host transition. Infect Immun 75:2864–2874PubMedCentralPubMedCrossRefGoogle Scholar
  57. Matsunaga J, Coutinho ML (2012) Positive regulation of Leptospira interrogans kdp expression by KdpE as demonstrated with a novel β-galactosidase reporter in Leptospira biflexa. Appl Environ Microbiol 78:5699–5707PubMedCentralPubMedCrossRefGoogle Scholar
  58. Monahan AM, Callanan JJ, Nally JE (2008) Proteomic analysis of Leptospira interrogans shed in urine of chronically infected hosts. Infect Immun 76:4952–4958PubMedCentralPubMedCrossRefGoogle Scholar
  59. Morero NR, Botti H, Nitta KR, Carrión F, Obal G, Picardeau M, Buschiazzo A (2014) HemR is an OmpR/PhoB-like response regulator from Leptospira, which simultaneously effects transcriptional activation and repression of key haem metabolism genes. Mol Microbiol. doi: 10.1111/mmi.12763
  60. Murray GL, Ellis KM, Lo M, Adler B (2008) Leptospira interrogans requires a functional heme oxygenase to scavenge iron from hemoglobin. Microbes Infect 10:791–797PubMedCrossRefGoogle Scholar
  61. Murray GL, Morel V, Cerqueira GM, Croda J, Srikram A, Henry R, Ko AI, Dellagostin OA, Bulach DM, Sermswan R, Adler B, Picardeau M (2009a) Genome-wide transposon mutagenesis in pathogenic Leptospira spp. Infect Immun 77:810–816PubMedCentralPubMedCrossRefGoogle Scholar
  62. Murray GL, Srikram A, Henry R, Puapairoj A, Sermswan RW, Adler B (2009b) Leptospira interrogans requires heme oxygenase for disease pathogenesis. Microbes Infect 11:311–314PubMedCrossRefGoogle Scholar
  63. Murray GL, Srikram A, Hoke DE, Wunder EAJ, Henry R, Lo M, Zhang K, Sermswan RW, Ko AI, Adler B (2009c) The major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans. Infect Immun 77:952–958PubMedCentralPubMedCrossRefGoogle Scholar
  64. Murray GL, King AM, Srikram A, Sermswan RW, Adler B (2010a) Use of luminescent Leptospira interrogans for enumeration in biological assays. J Clin Microbiol 48:2037–2042PubMedCentralPubMedCrossRefGoogle Scholar
  65. Murray GL, Srikram A, Henry R, Hartskeerl RA, Sermswan RW, Adler B (2010b) Mutations affecting Leptospira interrogans lipopolysaccharide attenuate virulence. Mol Microbiol 78:701–709PubMedCrossRefGoogle Scholar
  66. Nally JE, Artiushin S, Timoney JF (2001) Molecular characterization of thermoinduced immunogenic proteins Q1p42 and Hsp15 of Leptospira interrogans. Infect Immun 69:7616–7624PubMedCentralPubMedCrossRefGoogle Scholar
  67. Nally JE, Chow E, Fishbein MC, Blanco DR, Lovett MA (2005a) Changes in lipopolysaccharide O antigen distinguish acute versus chronic Leptospira interrogans infections. Infect Immun 73:3251–3260PubMedCentralPubMedCrossRefGoogle Scholar
  68. Nally JE, Whitelegge JP, Aguilera R, Pereira MM, Blanco DR, Lovett MA (2005b) Purification and proteomic analysis of outer membrane vesicles from a clinical isolate of Leptospira interrogans serovar Copenhageni. Proteomics 5:144–152PubMedCrossRefGoogle Scholar
  69. Nally JE, Whitelegge JP, Bassilian S, Blanco DR, Lovett MA (2007) Characterization of the outer membrane proteome of Leptospira interrogans expressed during acute lethal infection. Infect Immun 75:766–773PubMedCentralPubMedCrossRefGoogle Scholar
  70. Nascimento AL, Ko AI, Martins EA, Monteiro-Vitorello CB, Ho PL, Haake DA, Verjovski-Almeida S, Hartskeerl RA, Marques MV, Oliveira MC, Menck CF, Leite LC, Carrer H, Coutinho LL, Degrave WM, Dellagostin OA, El-Dorry H, Ferro ES, Ferro MI, Furlan LR, Gamberini M, Giglioti EA, Goes-Neto A, Goldman GH, Goldman MH, Harakava R, Jeronimo SM, Junqueira-de-Azevedo IL, Kimura ET, Kuramae EE, Lemos EG, Lemos MV, Marino CL, Nunes LR, de Oliveira RC, Pereira GG, Reis MS, Schriefer A, Siqueira WJ, Sommer P, Tsai SM, Simpson AJ, Ferro JA, Camargo LE, Kitajima JP, Setubal JC, Van Sluys MA (2004) Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis. J Bacteriol 186:2164–2172PubMedCentralPubMedCrossRefGoogle Scholar
  71. Patarakul K, Lo M, Adler B (2010) Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum. BMC Microbiol 10:31PubMedCentralPubMedCrossRefGoogle Scholar
  72. Picardeau M, Brenot A, Saint Girons I (2001) First evidence for gene replacement in Leptospira spp. Inactivation of L. biflexa flaB results in non-motile mutants deficient in endoflagella. Mol Microbiol 40:189–199PubMedCrossRefGoogle Scholar
  73. Picardeau M (2008) Conjugative transfer between Escherichia coli and Leptospira spp. as a new genetic tool. Appl Environ Microbiol 74:319–322PubMedCentralPubMedCrossRefGoogle Scholar
  74. Picardeau M, Bulach DM, Bouchier C, Zuerner RL, Zidane N, Wilson PJ, Creno S, Kuczek ES, Bommezzadri S, Davis JC, McGrath A, Johnson MJ, Boursaux-Eude C, Seemann T, Rouy Z, Coppel RL, Rood JI, Lajus A, Davies JK, Médigue C, Adler B (2008) Genome sequence of the saprophyte Leptospira biflexa provides insights into the evolution of Leptospira and the pathogenesis of leptospirosis. PLoS ONE 3:1607CrossRefGoogle Scholar
  75. Pinne M, Haake DA (2009) A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans. PLoS ONE 4:6071CrossRefGoogle Scholar
  76. Pinne M, Haake DA (2013) LipL32 is a subsurface lipoprotein of Leptospira interrogans: presentation of new data and reevaluation of previous studies. PLoS ONE 8:51025CrossRefGoogle Scholar
  77. Poggi D, Oliveirade Giuseppe P, Picardeau M (2010) Antibiotic resistance markers for genetic manipulations of Leptospira spp. Appl Environ Microbiol 76:4882–4885Google Scholar
  78. Qin JH, Sheng YY, Zhang ZM, Shi YZ, He P, Hu BY, Yang Y, Liu SG, Zhao GP, Guo XK (2006) Genome-wide transcriptional analysis of temperature shift in L. interrogans serovar lai strain 5660. BMC Microbiol 6:51PubMedCentralPubMedCrossRefGoogle Scholar
  79. Qin JH, Zhang Q, Zhang ZM, Zhong Y, Yang Y, Hu BY, Zhao GP, Guo XK (2008) Identification of a novel prophage-like gene cluster actively expressed in both virulent and avirulent strains of Leptospira interrogans serovar Lai. Infect Immun 76:2411–2419PubMedCentralPubMedCrossRefGoogle Scholar
  80. Ren S, Fu G, Jiang X, Zeng R, Xiong H, Lu G, Jiang HQ, Miao Y, Xu H, Zhang Y, Guo X, Shen Y, Qiang BQ, Danchin A, Saint Girons I, Somerville RL, Weng YM, Shi M, Chen Z, Xu JG, Zhao GP (2003) Unique and physiological and pathogenic features of Leptospira interrogans revealed by whole genome sequencing. Nature 422:888–893Google Scholar
  81. Ricaldi JN, Fouts DE, Selengut JD, Harkins DM, Moreno A, Lehmann JS, Purushe J, Sanka R, Torres M, Webster NJ, Vinetz JM, Matthias MA (2012a) Whole genome analysis of Leptospira licerasiae provides insight into Leptospiral evolution and pathogenicity. PLoS Negl Trop Dis 6:1853CrossRefGoogle Scholar
  82. Ricaldi JN, Matthias MA, Vinetz JM, Lewis AL (2012b) Expression of sialic acids and other nonulosonic acids in Leptospira. BMC Microbiol 12:161PubMedCrossRefGoogle Scholar
  83. Richaud C, Margarita D, Baranton G, Saint Girons I (1990) Cloning of genes required for amino acid biosynthesis from Leptospira interrogans serovar icterohaemorrhagiae. J Gen Microbiol 136:651–656PubMedCrossRefGoogle Scholar
  84. Ristow P, Bourhy P, da Cruz McBride FW, Figueira CP, Huerre M, Ave P, Girons IS, Ko AI, Picardeau M (2007) The OmpA-like protein Loa22 is essential for Leptospiral virulence. PLoS Pathog 3:97CrossRefGoogle Scholar
  85. Saint Girons I, Margarita D, Amouriaux P, Baranton G (1990) First isolation of bacteriophages for a spirochaete: potential genetic tools for Leptospira. Res Microbiol 141:1131–1138PubMedCrossRefGoogle Scholar
  86. Saint Girons I, Norris SJ, Gobel U, Meyer J, Walker EM, Zuerner R (1992) Genome structure of spirochetes. Res Microbiol 143:615–621PubMedCrossRefGoogle Scholar
  87. Saint Girons I, Bourhy P, Ottone C, Picardeau M, Yelton D, Hendrix RW, Glaser P, Charon N (2000) The LE1 bacteriophage replicates as a plasmid within Leptospira biflexa: construction of an L. biflexa-Escherichia coli shuttle vector. J Bacteriol 182:5700–5705CrossRefGoogle Scholar
  88. Seshadri R, Myers GS, Tettelin H, Eisen JA, Heidelberg JF, Dodson RJ, Davidsen TM, DeBoy RT, Fouts DE, Haft DH, Selengut J, Ren Q, Brinkac LM, Madupu R, Kolonay J, Durkin SA, Daugherty SC, Shetty J, Shvartsbeyn A, Gebregeorgis E, Geer K, Tsegaye G, Malek J, Ayodeji B, Shatsman S, McLeod MP, Smajs D, Howell JK, Pal S, Amin A, Vashisth P, McNeill TZ, Xiang Q, Sodergren E, Baca E, Weinstock GM, Norris SJ, Fraser CM, Paulsen IT (2004) Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes. Proc Natl Acad Sci USA 101:5646–5651PubMedCentralPubMedCrossRefGoogle Scholar
  89. Slamti L, de Pedro MA, Guichet E, Picardeau M (2011) Deciphering morphological determinants of the helix-shaped Leptospira. J Bacteriol 193:6266–6275PubMedCentralPubMedCrossRefGoogle Scholar
  90. Stamm LV, Parrish EA, Gherardini FC (1991) Cloning of the recA gene from a free-living leptospire and distribution of RecA-like protein among spirochetes. Appl Environ Microbiol 57:183–189PubMedCentralPubMedGoogle Scholar
  91. Ulrich LE, Zhulin IB (2010) The MiST2 database: a comprehensive genomics resource on microbial signal transduction. Nucleic Acids Res 38:401–407CrossRefGoogle Scholar
  92. Xue F, Dong H, Wu J, Wu Z, Hu W, Sun A, Troxell B, Yang XF, Yan J (2010) Transcriptional responses of Leptospira interrogans to host innate immunity: significant changes in metabolism, oxygen tolerance, and outer membrane. PLoS Negl Trop Dis 4(10):e857Google Scholar
  93. Yelton DB, Cohen RA (1986) Analysis of cloned DNA from Leptospira biflexa serovar patoc which complements a deletion of the Escherichia coli trpE gene. J Bacteriol 165:41–46PubMedCentralPubMedGoogle Scholar
  94. Zhang C, Wang H, Yan J (2012a) Leptospirosis prevalence in Chinese populations in the last two decades. Microbes Infect 14:317–323PubMedCrossRefGoogle Scholar
  95. Zhang K, Murray GL, Seemann T, Srikram A, Bartpho T, Sermswan RW, Adler B, Hoke DE (2013). Leptospiral LruA is required for virulence and modulates an interaction with mammalian Apolipoprotein A-I. Infect Imm 8:3872–3879Google Scholar
  96. Zhang L, Zhang C, Ojcius DM, Sun D, Zhao J, Lin X, Li L, Li L, Yan J (2012b) The mammalian cell entry (Mce) protein of pathogenic Leptospira species is responsible for RGD motif-dependent infection of cells and animals. Mol Microbiol 83:1006–1023PubMedCrossRefGoogle Scholar
  97. Zhong Y, Chang X, Cao XJ, Zhang Y, Zheng H, Zhu YZ, Cai C, Cui Z, Zhang Y, Li YY, Jiang XG, Zhao GP, Wang S, Li Y, Zeng R, Li X, Guo XK (2011) Comparative proteogenomic analysis of the Leptospira interrogans virulence-attenuated strain IPAV against the pathogenic strain 56601. Cell Res 21:1210–1229PubMedCentralPubMedCrossRefGoogle Scholar
  98. Zuerner RL (1991) Physical mapping of chromosomal and plasmid DNA comprising the genome of Leptospira interrogans. Nucleic Acids Res 19:4857–4860PubMedCentralPubMedCrossRefGoogle Scholar
  99. Zuerner RL, Herrmann JL, Saint Girons I (1993) Comparison of genetic maps for two Leptospira interrogans serovars provides evidence for two chromosomes and intraspecies heterogeneity. J Bacteriol 175:5445–5451PubMedCentralPubMedGoogle Scholar
  100. Zuerner RL (1994) Nucleotide sequence analysis of IS1533 from Leptospira borgpetersenii: identification and expression of two IS-encoded proteins. Plasmid 31:1–11PubMedCrossRefGoogle Scholar
  101. Zuerner RL, Huang WM (2002) Analysis of a Leptospira interrogans locus containing DNA replication genes and a new IS, IS1502. FEMS Microbiol Lett 215:175–182PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.“Biology of Spirochetes” Unit, Institut PasteurParis Cedex 15France

Personalised recommendations