Abstract
The outer membrane (OM) is the front line of leptospiral interactions with their environment and the mammalian host. Unlike most invasive spirochetes, pathogenic leptospires must be able to survive in both free-living and host-adapted states. As organisms move from one set of environmental conditions to another, the OM must cope with a series of conflicting challenges. For example, the OM must be porous enough to allow nutrient uptake, yet robust enough to defend the cell against noxious substances. In the host, the OM presents a surface decorated with adhesins and receptors for attaching to, and acquiring, desirable host molecules such as the complement regulator, Factor H. On the other hand, the OM must enable leptospires to evade detection by the host’s immune system on their way from sites of invasion through the bloodstream to the protected niche of the proximal tubule. The picture that is emerging of the leptospiral OM is that, while it shares many of the characteristics of the OMs of spirochetes and Gram-negative bacteria, it is also unique and different in ways that make it of general interest to microbiologists. For example, unlike most other pathogenic spirochetes, the leptospiral OM is rich in lipopolysaccharide (LPS). Leptospiral LPS is similar to that of Gram-negative bacteria but has a number of unique structural features that may explain why it is not recognized by the LPS-specific Toll-like receptor 4 of humans. As in other spirochetes, lipoproteins are major components of the leptospiral OM, though their roles are poorly understood. The functions of transmembrane outer membrane proteins (OMPs) in many cases are better understood, thanks to homologies with their Gram-negative counterparts and the emergence of improved genetic techniques. This chapter will review recent discoveries involving the leptospiral OM and its role in leptospiral physiology and pathogenesis.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Asuthkar S, Velineni S, Stadimann J, Altmann F, Sritharan M (2007) Expression and characterization of an iron-regulated hemin-binding protein, HbpA, from Leptospira interrogans serovar Lai. Infect Immun 75:4582–4591
Bagos PG, Liakopoulos TD, Spyropoulos IC, Hamodrakas SJ (2004) PRED-TMBB: a web server for predicting the topology of beta-barrel outer membrane proteins. Nucleic Acids Res 32:W400–W404
Barbosa AS, Abreu PA, Neves FO, Atzingen MV, Watanabe MM, Vieira ML, Morais ZM, Vasconcellos SA, Nascimento AL (2006) A newly identified leptospiral adhesin mediates attachment to laminin. Infect Immun 74:6356–6364
Barnett JK, Barnett D, Bolin CA, Summers TA, Wagar EA, Cheville NF, Hartskeerl RA, Haake DA (1999) Expression and distribution of leptospiral outer membrane components during renal infection of hamsters. Infect Immun 67:853–861
Bos MP, Robert V, Tommassen J (2007) Biogenesis of the gram-negative bacterial outer membrane. Annu Rev Microbiol 61:191–214
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 20:197–210
Castiblanco-Valencia MM, Fraga TR, Silva LB, Monaris D, Abreu PA, Strobel S, Jozsi M, Isaac L, Barbosa AS (2012) Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP. J Infect Dis 205:995–1004
Chen S, Zückert WR (2011) Probing the Borrelia burgdorferi surface lipoprotein secretion pathway using a conditionally folding protein domain. J Bacteriol 193:6724–6732
Choy HA (2012) Multiple activities of LigB potentiate virulence of Leptospira interrogans: inhibition of alternative and classical pathways of complement. PLoS ONE 7:e41566
Choy HA, Kelley MM, Chen TL, Moller AK, Matsunaga J, Haake DA (2007) Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen. Infect Immun 75:2441–2450
Choy HA, Kelley MM, Croda J, Matsunaga J, Babbitt JT, Ko AI, Picardeau M, Haake DA (2011) The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans. PLoS ONE 6:e16879
Coutinho ML, Choy HA, Haake D (2011) A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans. PLoS Neg Trop Dis 5:e1422
Cowles CE, Li Y, Semmelhack MF, Cristea IM, Silhavy TJ (2011) The free and bound forms of Lpp occupy distinct subcellular locations in Escherichia coli. Mol Microbiol 79:1168–1181
Croda J, Ramos JG, Matsunaga J, Queiroz A, Homma A, Riley LW, Haake DA, Reis MG, Ko AI (2007) Leptospira immunoglobulin-like proteins as a serodiagnostic marker for acute leptospirosis. J Clin Microbiol 45:1528–1534
Cullen PA, Cordwell SJ, Bulach DM, Haake DA, Adler B (2002) Global analysis of outer membrane proteins from Leptospira interrogans serovar Lai. Infect Immun 70:2311–2318
Cullen PA, Haake DA, Bulach DM, Zuerner RL, Adler B (2003) LipL21 is a novel surface-exposed lipoprotein of pathogenic Leptospira species. Infect Immun 71:2414–2421
Cullen PA, Xu X, Matsunaga J, Sanchez Y, Ko AI, Haake DA, Adler B (2005) Surfaceome of Leptospira spp. Infect Immun 73:4853–4863
d’Enfert C, Ryter A, Pugsley AP (1987) Cloning and expression in Escherichia coli of the Klebsiella pneumoniae genes for production, surface localization and secretion of the lipoprotein pullulanase. EMBO J 6:3531–3538
Deveson Lucas DS, Cullen PA, Lo M, Srikram A, Sermswan RW, Adler B (2011) Recombinant LipL32 and LigA from Leptospira are unable to stimulate protective immunity against leptospirosis in the hamster model. Vaccine 29:3413–3418
Dong C, Beis K, Nesper J, Brunkan-LaMontagne AL, Clarke BR, Whitfield C, Naismith JH (2006) Wza the translocon for E. coli capsular polysaccharides defines a new class of membrane protein. Nature 444:226–229
Eshghi A, Cullen PA, Cowen L, Zuerner RL, Cameron CE (2009) Global proteome analysis of Leptospira interrogans. J Proteome Res 8:4564–4578
Eshghi A, Pinne M, Haake DA, Zuerner RL, Frank A, Cameron CE (2012) Methylation and in vivo expression of the surface-exposed Leptospira interrogans outer membrane protein OmpL32. Microbiol 158:622–635
Farrelly HE, Adler B, Faine S (1987) Opsonic monoclonal antibodies against lipopolysaccharide antigens of Leptospira interrogans serovar hardjo. J Med Microbiol 23:1–7
Fernandes LG, Vieira ML, Kirchgatter K, Alves IJ, de Morais ZM, Vasconcellos SA, Romero EC, Nascimento AL (2012) OmpL1 is an extracellular matrix- and plasminogen-interacting protein of Leptospira spp. Infect Immun 80:3679–3692
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 extracellular matrix components. BMC Microbiol 11:129
Giuseppe PO, Von Atzingen M, Nascimento AL, Zanchin NI, Guimaraes BG (2011) The crystal structure of the leptospiral hypothetical protein LIC12922 reveals homology with the periplasmic chaperone SurA. J Struct Biol 173:312–322
Gromiha MM, Suwa M (2005) A simple statistical method for discriminating outer membrane proteins with better accuracy. Bioinformatics 21:961–968
Haake DA (2000) Spirochaetal lipoproteins and pathogenesis. Microbiol 146:1491–1504
Haake DA, Matsunaga J (2002) Characterization of the leptospiral outer membrane and description of three novel leptospiral membrane proteins. Infect Immun 70:4936–4945
Haake DA, Walker EM, Blanco DR, Bolin CA, Miller MN, Lovett MA (1991) Changes in the surface of Leptospira interrogans serovar grippotyphosa during in vitro cultivation. Infect Immun 59:1131–1140
Haake DA, Champion CI, Martinich C, Shang ES, Blanco DR, Miller JN, Lovett MA (1993) Molecular cloning and sequence analysis of the gene encoding OmpL1, a transmembrane outer membrane protein of pathogenic Leptospira spp. J Bacteriol 175:4225–4234
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 66:1579–1587
Haake DA, Mazel MK, McCoy AM, Milward F, Chao G, Matsunaga J, Wagar EA (1999) Leptospiral outer membrane proteins OmpL1 and LipL41 exhibit synergistic immunoprotection. Infect Immun 67:6572–6582
Haake DA, Chao G, Zuerner RL, Barnett JK, Barnett D, Mazel M, Matsunaga J, Levett PN, Bolin CA (2000) The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun 68:2276–2285
Haake DA, Suchard MA, Kelley MM, Dundoo M, Alt DP, Zuerner RL (2004) Molecular evolution and mosaicism of leptospiral outer membrane proteins involves horizontal DNA transfer. J Bacteriol 186:2818–2828
Hauk P, Guzzo CR, Roman Ramos H, Ho PL, Farah CS (2009) Structure and calcium-binding activity of LipL32, the major surface antigen of pathogenic Leptospira sp. J Mol Biol 390:722–736
Hauk P, Barbosa AS, Ho PL, Farah CS (2012) Calcium binding to leptospira outer membrane antigen LipL32 is not necessary for its interaction with plasma fibronectin, collagen type IV, and plasminogen. J Biol Chem 287:4826–4834
Jost BH, Adler B, Faine S (1989) Experimental immunisation of hamsters with lipopolysaccharide antigens of Leptospira interrogans. J Med Microbiol 29:115–120
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 protein, Lep, for stable expression. Infect Immun 81:2768–2776
Koizumi N, Watanabe H (2003) Molecular cloning and characterization of a novel leptospiral lipoprotein with OmpA domain. FEMS Microbiol Lett 226:215–219
Kovacs-Simon A, Titball RW, Michell SL (2011) Lipoproteins of bacterial pathogens. Infect Immun 79:548–561
Kropinski AM, Parr TR Jr, Angus BL, Hancock RE, Ghiorse WC, Greenberg EP (1987) Isolation of the outer membrane and characterization of the major outer membrane protein from Spirochaeta aurantia. J Bacteriol 169:172–179
Kumru OS, Schulze RJ, Slusser JG, Zückert WR (2010) Development and validation of a FACS-based lipoprotein localization screen in the Lyme disease spirochete Borrelia burgdorferi. BMC Microbiol 10:277
Kumru OS, Schulze RJ, Rodnin MV, Ladokhin AS, Zuckert WR (2011) Surface localization determinants of Borrelia OspC/Vsp family lipoproteins. J Bacteriol 193:2814–2825
Lee PA, Tullman-Ercek D, Georgiou G (2006) The bacterial twin-arginine translocation pathway. Annu Rev Microbiol 60:373–395
Lessa-Aquino C, Borges Rodrigues C, Pablo J, Sasaki R, Jasinskas A, Liang L, Wunder EA Jr, Ribeiro GS, Vigil A, Galler R, Molina D, Liang X, Reis MG, Ko AI, Medeiros MA, Felgner PL (2013) Identification of seroreactive proteins of Leptospira interrogans serovar Copenhageni using a high-density protein microarray approach. PLoS Negl Trop Dis 7:e2499
Lin MH, Chang YC, Hsiao CD, Huang SH, Wang MS, Ko YC, Yang CW, Sun YJ (2013) LipL41, a hemin binding protein from Leptospira santarosai serovar Shermani. PLoS ONE 8:e83246
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 74:5848–5859
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:e560
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 78:4850–4859
Lourdault K, Wang LC, Vieira A, Matsunaga J, Melo R, Lewis MS, Haake DA, Gomes-Solecki M (2014) Oral immunization with E. coli expressing a lipidated form of LigA protects hamsters against challenge with Leptospira interrogans serovar Copenhageni. Infect Immun doi:10.1128/IAI.01533-13
Louvel H, Bommezzadri S, Zidane N, Boursaux-Eude C, Creno S, Magnier A, Rouy Z, Médigue C, Saint Girons I, Bouchier C, Picardeau M (2006) Comparative and functional genomic analyses of iron transport and regulation in Leptospira spp. J Bacteriol 188:7893–7904
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 460:762–766
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 78:6372–6376
Matsunaga J, Young TA, Barnet JK, Barnett D, Bolin CA, Haake DA (2002) Novel 45-kilodalton leptospiral protein that is processed to a 31-kilodalton growth-phase-regulated peripheral membrane protein. Infect Immun 70:323–334
Matsunaga J, Barocchi MA, Croda J, Young TA, Sanchez Y, Siqueira I, Bolin CA, Reis MG, Riley LW, Haake DA, Ko AI (2003) Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily. Mol Microbiol 49:929–945
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 73:70–78
Matsunaga J, Wernied K, Zuerner R, Frank A, Haake, DA (2006) LipL46 is a novel, surface-exposed lipoprotein expressed during leptospiral dissemination in the mammalian host. Microbiol 152, 3777–3786
Matsunaga J, Lo M, Bulach DM, Zuerner RL, Adler B, Haake DA (2007a) Response of Leptospira interrogans to physiologic osmolarity: relevance in signaling the environment-to-host transition. Infect Immun 75:2864–2874
Matsunaga J, Medeiros MA, Sanchez Y, Werneid KF, Ko AI (2007b) Osmotic regulation of expression of two extracellular matrix-binding proteins and a haemolysin of Leptospira interrogans: differential effects on LigA and Sph2 extracellular release. Microbiol 153:3390–3398
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 195:5092–5101
McBride AJ, Cerqueira GM, Suchard MA, Moreira AN, Zuerner RL, Reis MG, Haake DA, Ko AI, Dellagostin OA (2009) Genetic diversity of the leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp. Infect Genet Evol 9:196–205
Midwinter AC, Vinh T, Faine S, Adler B (1994) Characterization of an antigenic oligosaccharide from Leptospira interrogans serovar pomona and its role in immunity. Infect Immun 62:5477–5482
Murray GL (2013) The lipoprotein LipL32, an enigma of leptospiral biology. Vet Microbiol 162:305–314
Murray GL, Morel V, Cerqueira GM, Croda J, Srikram A, Henry R, Ko AI, Dellagostin OA, Bulach DM, Sermswan RW, Adler B, Picardeau M (2009a) Genome-wide transposon mutagenesis in pathogenic Leptospira species. Infect Immun 77:810–816
Murray GL, Srikram A, Hoke DE, Wunder EA Jr, Henry R, Lo M, Zhang K, Sermswan RW, Ko AI, Adler B (2009b) Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans. Infect Immun 77:952–958
Murray GL, Srikram A, Henry R, Hartskeerl RA, Sermswan RW, Adler B (2010) Mutations affecting Leptospira interrogans lipopolysaccharide attenuate virulence. Mol Microbiol 78:701–709
Nahori MA, Fournie-Amazouz E, Que-Gewirth NS, Balloy V, Chignard M, Raetz CR, Saint Girons I, Werts C (2005) Differential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells. J Immunol 175:6022–6031
Nally JE, Artiushin S, Timoney JF (2001a) Molecular characterization of thermoinduced immunogenic proteins Q1p42 and Hsp15 of Leptospira interrogans. Infect Immun 69:7616–7624
Nally JE, Timoney JF, Stevenson B (2001b) Temperature-regulated protein synthesis by Leptospira interrogans. Infect Immun 69:400–404
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 73:3251–3260
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 5:144–152
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 75:766–773
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, Góes-Neto A, Goldman GH, Goldman MH, Harakava R, Jerônimo 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 186:2164–2172
Oke M, Sarra R, Ghirlando R, Farnaud S, Gorringe AR, Evans RW, Buchanan SK (2004) The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane beta-barrel. FEBS lett 564:294–300
Oliveira TR, Longhi MT, Goncales AP, de Morais ZM, Vasconcellos SA, Nascimento AL (2010) LipL53, a temperature regulated protein from Leptospira interrogans that binds to extracellular matrix molecules. Microbes Infect 12:207–217
Oliveira R, de Morais ZM, Goncales AP, Romero EC, Vasconcellos SA, Nascimento AL (2011) Characterization of novel OmpA-like protein of Leptospira interrogans that binds extracellular matrix molecules and plasminogen. PLoS ONE 6:e21962
Patarakul K, Lo M, Adler B (2010) Global transcriptomic response of Leptospira interrogans serovar Copenhageni upon exposure to serum. BMC Microbiol 10:31
Pinne M, Haake DA (2009) A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans. PLoS ONE 4:e6071
Pinne M, Haake DA (2011) Detection of leptospiral surface-exposed proteins via immunofluorescence. J Vis Exp 53:2805
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:e51025
Pinne M, Matsunaga J, Haake DA (2012) A novel approach to identification of leptospiral ligand-binding proteins: an outer-membrane protein microarray. J Bacteriol 194:6074–6087
Pomorski T, Menon AK (2006) Lipid flippases and their biological functions. Cell Mol Life Sci 63:2908–2921
Que-Gewirth NS, Riberio AA, Kalb SR, Cotter RJ, Bulach DM, Adler B, Saint Girons I, Werts C, Raetz CR (2004) A methylated phosphate group and four amide-linked acyl chains in Leptospira interrogans Lipid A. J Biol Chem 279:25420–25429
Raddi G, Morado DR, Yan J, Haake DA, Yang XF, Liu J (2012) Three-dimensional structures of pathogenic and saprophytic Leptospira species revealed by cryo-electron tomography. J Bacteriol 194:1299–1306
Radolf JD, Norgard MV, Schulz WW (1989) Outer membrane ultrastructure explains the limited antigenicity of virulent Treponema pallidum. Proc Natl Acad Sci USA 86:2051–2055
Ren SX, Fu G, Jiang XG, Zeng R, Miao YG, Xu H, Zhang YX, Xiong H, Lu G, Lu LF, Jiang HQ, Jia J, Tu YF, Jiang JX, Gu WY, Zhang YQ, Cai Z, Sheng HH, Yin HF, Zhang Y, Zhu GF, Wan M, Huang HL, Qian Z, Wang SY, Ma W, Yao ZJ, Shen Y, Qiang BQ, Xia QC, Guo XK, Danchin A, Saint Girons I, Somerville RL, Wen YM, Shi MH, Chen Z, Xu JG, Zhao GP (2003) Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing. Nature 422:888–893
Ristow P, Bourhy P, da Cruz McBride FW, Figueira CP, Huerre M, Ave P, Saint Girons I, Ko AI, Picardeau M (2007) The OmpA-like protein Loa22 is essential for leptospiral virulence. PLoS Pathog 3:e97
Ruiz N, Kahne D, Silhavy TJ (2009) Transport of lipopolysaccharide across the cell envelope: the long road of discovery. Nat Rev Microbiol 7:677–683
Sauvonnet N, Pugsley AP (1996) Identification of two regions of Klebsiella oxytoca pullulanase that together are capable of promoting beta-lactamase secretion by the general secretory pathway. Mol Microbiol 22:1–7
Schauer K, Rodionov DA, de Reuse H (2008) New substrates for TonB-dependent transport: do we only see the ‘tip of the iceberg’? Trends Biochem Sci 33:330–338
Schulze RJ, Zuckert WR (2006) Borrelia burgdorferi lipoproteins are secreted to the outer surface by default. Mol Microbiol 59:1473–1484
Schulze RJ, Chen S, Kumru OS, Zückert WR (2010) Translocation of Borrelia burgdorferi surface lipoprotein OspA through the outer membrane requires an unfolded conformation and can initiate at the C-terminus. Mol Microbiol 76:1266–1278
Setubal JC, Reis M, Matsunaga J, Haake DA (2006) Lipoprotein computational prediction in spirochaetal genomes. Microbiol 152:113–121
Shang ES, Exner MM, Summers TA, Martinich C, Champion CI, Hancock RE, Haake DA (1995) The rare outer membrane protein, OmpL1, of pathogenic Leptospira species is a heat-modifiable porin. Infect Immun 63:3174–3181
Shang ES, Summers TA, Haake DA (1996) Molecular cloning and sequence analysis of the gene encoding LipL41, a surface-exposed lipoprotein of pathogenic Leptospira species. Infect Immun 64:2322–2330
Silva EF, Medeiros MA, McBride AJ, Matsunaga J, Esteves GS, Ramos JG, Santos CS, Croda J, Homma A, Dellagostin OA, Haake DA, Reis MG, Ko AI (2007) The terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis. Vaccine 25:6277–6286
Sklar JG, Wu T, Kahne D, Silhavy TJ (2007) Defining the roles of the periplasmic chaperones SurA, Skp, and DegP in Escherichia coli. Genes Develop 21:2473–2484
Sperandeo P, Deho G, Polissi A (2009) The lipopolysaccharide transport system of Gram-negative bacteria. Biochim Biophys Acta 1791:594–602
Srikram A, Zhang K, Bartpho T, Lo M, Hoke DE, Sermswan RW, Adler B, Murray GL (2011) Cross-protective immunity against leptospirosis elicited by a live, attenuated lipopolysaccharide mutant. J Infect Dis 203:870–879
Stevenson B, Choy HA, Pinne M, Rotondi ML, Miller MC, Demoll E, Kraiczy P, Cooley AE, Creamer TP, Suchard MA, Brissette CA, Verma A, Haake DA (2007) Leptospira interrogans endostatin-like outer membrane proteins bind host fibronectin, laminin and regulators of complement. PLoS ONE 2:e1188
Tommassen J (2007) Getting into and through the outer membrane. Science 317:903–904
Verma A, Artiushin S, Matsunaga J, Haake DA, Timoney JF (2005) LruA and LruB, novel lipoproteins of pathogenic Leptospira interrogans associated with equine recurrent uveitis. Infect Immun 73:7259–7266
Verma A, Hellwage J, Artiushin S, Zipfel PF, Kraiczy P, Timoney JF, Stevenson B (2006) LfhA, a novel factor H-binding protein of Leptospira interrogans. Infect Immun 74:2659–2666
Verma A, Brissette CA, Bowman AA, Shah ST, Zipfel PF, Stevenson B (2010) Leptospiral endostatin-like protein A (LenA) is a bacterial cell-surface receptor for human plasminogen. Infect Immun 78:2053–2059
Vieira ML, Atzingen MV, Oliveira R, Mendes RS, Domingos RF, Vasconcellos S, Nascimento AL (2012) Plasminogen binding proteins and plasmin generation on the surface of Leptospira spp.: the contribution to the bacteria-host interactions. J Biomed Biotechnol 2012:758513
Viriyakosol S, Matthias MA, Swancutt MA, Kirkland TN, Vinetz JM (2006) Toll-like receptor 4 protects against lethal Leptospira interrogans serovar icterohaemorrhagiae infection and contributes to in vivo control of leptospiral burden. Infect Immun 74:887–895
Vivian JP, Beddoe T, McAlister AD, Wilce MC, Zaker-Tabrizi L, Troy S, Byres E, Hoke DE, Cullen PA, Lo M, Murray GL, Adler B, Rossjohn J (2009) Crystal structure of LipL32, the most abundant surface protein of pathogenic Leptospira spp. J Mol Biol 387:1229–1238
Walker EM, Borenstein LA, Blanco DR, Miller JN, Lovett MA (1991) Analysis of outer membrane ultrastructure of pathogenic Treponema and Borrelia species by freeze-fracture electron microscopy. J Bacteriol 173:5585–5588
Werts C (2010) Leptospirosis: a Toll road from B lymphocytes. Chang Gung Med J 3:591–601
Werts C, Tapping RI, Mathison JC, Chuang TH, Kravchenko V, Saint Girons I, Haake DA, Godowski PJ, Hayashi F, Ozinsky A, Underhill DM, Kirschning CJ, Wagner H, Aderem A, Tobias PS, Ulevitch RJ (2001) Leptospiral endotoxin activates cells via a TLR2-dependent mechanism. Nature Immunol 2:346–352
Wunder EA Jr, Figueira CP, Benaroudj N, Hu B, Tong BA, Trajtenberg F, Liu J, Reis MG, Charon N, Buschiazzo A, Picardeau M, Ko AI (2013) Leptospira Fcp1 is a key protein in determining the coiled morphology of purified flagella and conferring translational motility and virulence for the spirochete. In: 8th Scientific Meeting of the International Leptospirosis Society, Fukuoka, Japan
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:e857
Yakushi T, Masuda K, Narita S, Matsuyama S, Tokuda H (2000) A new ABC transporter mediating the detachment of lipid-modified proteins from membranes. Nat Cell Biol 2:212–218
Yang CW, Wu MS, Pan MJ, Hsieh WJ, Vandewalle A, Huang CC (2002) The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells. J Am Soc Nephrol 13:2037–2045
Yang CW, Hung CC, Wu MS, Tian YC, Chang CT, Pan MJ, Vandewalle A (2006) Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane proteins in proximal tubule cells. Kidney Int 69:815–822
Yokota N, Kuroda T, Matsuyama S, Tokuda H (1999) Characterization of the LolA-LolB system as the general lipoprotein localization mechanism of Escherichia coli. J Biol Chem 274:30995–30999
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 AI. Infect Immun 81:3872–3879
Zuerner RL, Knudtson W, Bolin CA, Trueba G (1991) Characterization of outer membrane and secreted proteins of Leptospira interrogans serovar pomona. Microb Pathog 10:311–322
Acknowledgments
The authors are extremely grateful to Dr. James Matsunaga for his helpful comments on regulation of Lig expression. Current work in Dr. Haake’s laboratory is supported by NIH Grant R01 AI034431 and a VA Merit Award. Current work in Dr. Zückert’s laboratory is supported by NIH Grant P30 GM103326 and a University of Kansas Medical Center Research Institute Lied Basic Science Pilot Grant.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Haake, D.A., Zückert, W.R. (2015). The Leptospiral Outer Membrane. In: Adler, B. (eds) Leptospira and Leptospirosis. Current Topics in Microbiology and Immunology, vol 387. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45059-8_8
Download citation
DOI: https://doi.org/10.1007/978-3-662-45059-8_8
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-45058-1
Online ISBN: 978-3-662-45059-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)