全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用：99美元
投递稿件

查看量下载量

相关文章

更多...
PLOS ONE  2013 

Leptospira interrogans Enolase Is Secreted Extracellularly and Interacts with Plasminogen

DOI: 10.1371/journal.pone.0078150

Full-Text   Cite this paper   Add to My Lib

Abstract:

Leptospira interrogans is the agent for leptospirosis, an important zoonosis in humans and animals across the globe. Surface proteins of invading pathogens, such as L. interrogans, are thought to be responsible for successful microbial persistence in vivo via interaction with specific host components. In particular, a number of invasive infectious agents exploit host proteolytic pathways, such as one involving plasminogen (Pg), which aid in efficient pathogen dissemination within the host. Here we show that L. interrogans serovar Lai binds host Pg and that the leptospiral gene product LA1951, annotated as enolase, is involved in this interaction. Interestingly, unlike in related pathogenic Spirochetes, such as Borrelia burgdorferi, LA1951 is not readily detectable in the L. interrogans outer membrane. We show that the antigen is indeed secreted extracellularly; however, it can reassociate with the pathogen surface, where it displays Pg-binding and measurable enzymatic activity. Hamsters infected with L. interrogans also develop readily detectable antibody responses against enolase. Taken together, our results suggest that the L. interrogans enolase has evolved to play a role in pathogen interaction with host molecules, which may contribute to the pathogenesis of leptospirosis.

 References

[1]  Adler B, de la Pe？a Moctezuma A (2010) Leptospira and leptospirosis. Vet Microbiol 140: 287-296. doi:10.1016/j.vetmic.2009.03.012. PubMed: 19345023.
[2]  Ko AI, Goarant C, Picardeau M (2009) Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen. Nat Rev Microbiol 7: 736-747. doi:10.1038/nrmicro2208. PubMed: 19756012.
[3]  Levett PN (2001) Leptospirosis. Clin Microbiol Rev 14: 296-326. doi:10.1128/CMR.14.2.296-326.2001. PubMed: 11292640.
[4]  Haake DA, Dundoo M, Cader R, Kubak BM, Hartskeerl RA et al. (2002) Leptospirosis, water sports, and chemoprophylaxis. Clin Infect Dis 34: e40-e43. doi:10.1086/339942. PubMed: 11941571.
[5]  Palaniappan RU, Ramanujam S, Chang YF (2007) Leptospirosis: pathogenesis, immunity, and diagnosis. Curr Opin Infect Dis 20: 284-292. doi:10.1097/QCO.0b013e32814a5729. PubMed: 17471039.
[6]  Cinco M (2010) New insights into the pathogenicity of leptospires: evasion of host defences. New Microbiol 33: 283-292. PubMed: 21213586.
[7]  Ko AI, Galv？o Reis M, Ribeiro Dourado CM, Johnson WD Jr., Riley LW (1999) Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group. Lancet 354: 820-825. doi:10.1016/S0140-6736(99)80012-9. PubMed: 10485724.
[8]  Reis RB, Ribeiro GS, Felzemburgh RD, Santana FS, Mohr S et al. (2008) Impact of environment and social gradient on Leptospira infection in urban slums. PLoS Negl Trop. Drosophila Inf Serv 2: e228.
[9]  Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM et al. (2003) Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis 3: 757-771. doi:10.1016/S1473-3099(03)00830-2. PubMed: 14652202.
[10]  Levett PN, Branch SL, Whittington CU, Edwards CN, Paxton H (2001) Two methods for rapid serological diagnosis of acute leptospirosis. Clin Diagn Lab Immunol 8: 349-351. PubMed: 11238220.
[11]  Palaniappan RU, Chang YF, Chang CF, Pan MJ, Yang CW et al. (2005) Evaluation of lig-based conventional and real time PCR for the detection of pathogenic leptospires. Mol Cell Probes 19: 111-117. doi:10.1016/j.mcp.2004.10.002. PubMed: 15680212.
[12]  Adler B, Lo M, Seemann T, Murray GL (2011) Pathogenesis of leptospirosis: the influence of genomics. Vet Microbiol 153: 73-81. doi:10.1016/j.vetmic.2011.02.055. PubMed: 21440384.
[13]  Barbosa AS, Abreu PA, Neves FO, Atzingen MV, Watanabe MM et al. (2006) A newly identified leptospiral adhesin mediates attachment to laminin. Infect Immun 74: 6356-6364. doi:10.1128/IAI.00460-06. PubMed: 16954400.
[14]  Chang YF, Chen CS, Palaniappan RU, He H, McDonough SP et al. (2007) Immunogenicity of the recombinant leptospiral putative outer membrane proteins as vaccine candidates. Vaccine 25: 8190-8197. doi:10.1016/j.vaccine.2007.09.020. PubMed: 17936448.
[15]  Cullen PA, Haake DA, Adler B (2004) Outer membrane proteins of pathogenic spirochetes. FEMS Microbiol Rev 28: 291-318. doi:10.1016/j.femsre.2003.10.004. PubMed: 15449605.
[16]  Lee SH, Kim S, Park SC, Kim MJ (2002) Cytotoxic activities of Leptospira interrogans hemolysin SphH as a pore-forming protein on mammalian cells. Infect Immun 70: 315-322. doi:10.1128/IAI.70.1.315-322.2002. PubMed: 11748197.
[17]  Merien F, Truccolo J, Baranton G, Perolat P (2000) Identification of a 36-kDa fibronectin-binding protein expressed by a virulent variant of Leptospira interrogans serovar icterohaemorrhagiae. FEMS Microbiol Lett 185: 17-22. doi:10.1111/j.1574-6968.2000.tb09034.x. PubMed: 10731601.
[18]  Ristow P, Bourhy P, da Cruz McBride FW, Figueira CP, Huerre M et al. (2007) The OmpA-like protein Loa22 is essential for leptospiral virulence. PLOS Pathog 3: e97. doi:10.1371/journal.ppat.0030097. PubMed: 17630832.
[19]  Vieira ML, Atzingen MV, Oliveira TR, Oliveira R, Andrade DM et al. (2010) In vitro identification of novel plasminogen-binding receptors of the pathogen Leptospira interrogans. PLOS ONE 5: e11259. doi:10.1371/journal.pone.0011259. PubMed: 20582320.
[20]  Cullen PA, Xu X, Matsunaga J, Sanchez Y, Ko AI et al. (2005) Surfaceome of Leptospira spp. Infect Immun 73: 4853-4863. doi:10.1128/IAI.73.8.4853-4863.2005. PubMed: 16040999.
[21]  Haake DA (2000) Spirochaetal lipoproteins and pathogenesis. Microbiology 146 ( 7): 1491-1504. PubMed: 10878114.
[22]  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. doi:10.1128/IAI.00741-06. PubMed: 17101664.
[23]  Vieira ML, Pimenta DC, de Morais ZM, Vasconcellos SA, Nascimento AL (2009) Proteome Analysis of Leptospira interrogans Virulent Strain. Open Microbiol J 3: 69-74. doi:10.2174/1874285800903010069. PubMed: 19590580.
[24]  Faisal SM, Yan W, Chen CS, Palaniappan RU, McDonough SP et al. (2008) Evaluation of protective immunity of Leptospira immunoglobulin like protein A (LigA) DNA vaccine against challenge in hamsters. Vaccine 26: 277-287. doi:10.1016/j.vaccine.2007.10.029. PubMed: 18055070.
[25]  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. doi:10.1128/IAI.70.5.2311-2318.2002. PubMed: 11953365.
[26]  Murray GL, Srikram A, Hoke DE, Wunder EA Jr., Henry R et al. (2009) Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans. Infect Immun 77: 952-958. doi:10.1128/IAI.01370-08. PubMed: 19103763.
[27]  Grassmann AA, Félix SR, dos Santos CX, Amaral MG, Neto Seixas et al. (2012) Protection against lethal leptospirosis after vaccination with LipL32 coupled or coadministered with the B subunit of Escherichia coli heat-labile enterotoxin. Clin Vaccine Immunol 19: 740-745. doi:10.1128/CVI.05720-11. PubMed: 22379066.
[28]  Rijken DC, Lijnen HR (2009) New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost 7: 4-13. doi:10.1111/j.1538-7836.2008.03220.x. PubMed: 19017261.
[29]  Plow EF, Herren T, Redlitz A, Miles LA, Hoover-Plow JL (1995) The cell biology of the plasminogen system. FASEB J 9: 939-945. PubMed: 7615163.
[30]  Vassalli JD, Sappino AP, Belin D (1991) The plasminogen activator/plasmin system. J Clin Invest 88: 1067-1072. doi:10.1172/JCI115405. PubMed: 1833420.
[31]  Mundodi V, Kucknoor AS, Alderete JF (2008) Immunogenic and plasminogen-binding surface-associated alpha-enolase of Trichomonas vaginalis. Infect Immun 76: 523-531. doi:10.1128/IAI.01352-07. PubMed: 18070902.
[32]  Miles LA, Dahlberg CM, Plescia J, Felez J, Kato K et al. (1991) Role of cell-surface lysines in plasminogen binding to cells: identification of alpha-enolase as a candidate plasminogen receptor. Biochemistry 30: 1682-1691. doi:10.1021/bi00220a034. PubMed: 1847072.
[33]  Bergmann S, Rohde M, Chhatwal GS, Hammerschmidt S (2001) alpha-Enolase of Streptococcus pneumoniae is a plasmin(ogen)-binding protein displayed on the bacterial cell surface. Mol Microbiol 40: 1273-1287. doi:10.1046/j.1365-2958.2001.02448.x. PubMed: 11442827.
[34]  Crowe JD, Sievwright IK, Auld GC, Moore NR, Gow NA et al. (2003) Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins. Mol Microbiol 47: 1637-1651. doi:10.1046/j.1365-2958.2003.03390.x. PubMed: 12622818.
[35]  Vieira ML, Vasconcellos SA, Gon？ales AP, de Morais ZM, Nascimento AL (2009) Plasminogen acquisition and activation at the surface of Leptospira species lead to fibronectin degradation. Infect Immun 77: 4092-4101. doi:10.1128/IAI.00353-09. PubMed: 19581392.
[36]  Verma A, Brissette CA, Bowman AA, Shah ST, Zipfel PF et al. (2010) Leptospiral endostatin-like protein A is a bacterial cell surface receptor for human plasminogen. Infect Immun 78: 2053-2059. doi:10.1128/IAI.01282-09. PubMed: 20160016.
[37]  Ren SX, Fu G, Jiang XG, Zeng R, Miao YG et al. (2003) Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing. Nature 422: 888-893. doi:10.1038/nature01597. PubMed: 12712204.
[38]  Nogueira SV, Smith AA, Qin JH, Pal U (2012) A surface enolase participates in Borrelia burgdorferi-plasminogen interaction and contributes to pathogen survival within feeding ticks. Infect Immun 80: 82-90. doi:10.1128/IAI.05671-11. PubMed: 22025510.
[39]  Pal U, Wang P, Bao F, Yang X, Samanta S et al. (2008) Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis. J Exp Med 205: 133-141. doi:10.1084/jem.20070962. PubMed: 18166585.
[40]  Haake DA, Chao G, Zuerner RL, Barnett JK, Barnett D et al. (2000) The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun 68: 2276-2285. doi:10.1128/IAI.68.4.2276-2285.2000. PubMed: 10722630.
[41]  Promnares K, Kumar M, Shroder DY, Zhang X, Anderson JF et al. (2009) Borrelia burgdorferi small lipoprotein Lp6.6 is a member of multiple protein complexes in the outer membrane and facilitates pathogen transmission from ticks to mice. Mol Microbiol 74: 112-125. doi:10.1111/j.1365-2958.2009.06853.x. PubMed: 19703109.
[42]  Yang X, Promnares K, Qin J, He M, Shroder DY et al. (2011) Characterization of multiprotein complexes of the Borrelia burgdorferi outer membrane vesicles. J Proteome Res 10: 4556-4566. doi:10.1021/pr200395b. PubMed: 21875077.
[43]  Jong AY, Chen SH, Stins MF, Kim KS, Tuan TL et al. (2003) Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells. J Med Microbiol 52: 615-622. doi:10.1099/jmm.0.05060-0. PubMed: 12867553.
[44]  Pancholi V, Fischetti VA (1998) alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci. J Biol Chem 273: 14503-14515. doi:10.1074/jbc.273.23.14503. PubMed: 9603964.
[45]  Agarwal S, Kulshreshtha P, Bambah Mukku D, Bhatnagar R (2008) alpha-Enolase binds to human plasminogen on the surface of Bacillus anthracis. Biochim Biophys Acta 1784: 986-994. doi:10.1016/j.bbapap.2008.03.017. PubMed: 18456007.
[46]  Chhatwal GS (2002) Anchorless adhesins and invasins of Gram-positive bacteria: a new class of virulence factors. Trends Microbiol 10: 205-208. doi:10.1016/S0966-842X(02)02351-X. PubMed: 11973142.
[47]  Floden AM, Watt JA, Brissette CA (2011) Borrelia burgdorferi enolase is a surface-exposed plasminogen binding protein. PLOS ONE 6: e27502. doi:10.1371/journal.pone.0027502. PubMed: 22087329.
[48]  Coleman JL, Gebbia JA, Piesman J, Degen JL, Bugge TH et al. (1997) Plasminogen is required for efficient dissemination of Borrelia burgdorferi in ticks and for enhancement of spirochetemia in mice. Cell 89: 1111-1119. doi:10.1016/S0092-8674(00)80298-6. PubMed: 9215633.
[49]  Coleman JL, Sellati TJ, Testa JE, Kew RR, Furie MB et al. (1995) Borrelia burgdorferi binds plasminogen, resulting in enhanced penetration of endothelial monolayers. Infect Immun 63: 2478-2484. PubMed: 7790059.
[50]  Fenno JC, Tamura M, Hannam PM, Wong GW, Chan RA et al. (2000) Identification of a Treponema denticola OppA homologue that binds host proteins present in the subgingival environment. Infect Immun 68: 1884-1892. doi:10.1128/IAI.68.4.1884-1892.2000. PubMed: 10722578.
[51]  Siqueira GH, Atzingen MV, Alves IJ, de Morais ZM, Vasconcellos SA et al. (2013) Characterization of Three Novel Adhesins of Leptospira interrogans. Am J Trop Med Hyg. PubMed: 23958908.
[52]  Yang CK, Ewis HE, Zhang X, Lu CD, Hu HJ et al. (2011) Nonclassical protein secretion by Bacillus subtilis in the stationary phase is not due to cell lysis. J Bacteriol 193: 5607-5615. doi:10.1128/JB.05897-11. PubMed: 21856851.
[53]  Zeng L, Zhang Y, Zhu Y, Yin H, Zhuang X et al. (2013) Extracellular Proteome Analysis of Leptospira interrogans serovar Lai. Omics. [Epub ahead of print]. doi:10.1089/omi.2013.0043. PubMed: 23895271.
[54]  Kornblatt MJ, Kornblatt JA, Hancock MA (2011) The interaction of canine plasminogen with Streptococcus pyogenes enolase: they bind to one another but what is the nature of the structures involved? PLOS ONE 6: e28481. doi:10.1371/journal.pone.0028481. PubMed: 22174817.
[55]  Nascimento AL, Ko AI, Martins EA, Monteiro-Vitorello CB, Ho PL et al. (2004) Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis. J Bacteriol 186: 2164-2172. doi:10.1128/JB.186.7.2164-2172.2004. PubMed: 15028702.
[56]  Bergmann S, Hammerschmidt S (2007) Fibrinolysis and host response in bacterial infections. Thromb Haemost 98: 512-520. PubMed: 17849039.
[57]  Goto H, Kawaoka Y (1998) A novel mechanism for the acquisition of virulence by a human influenza A virus. Proc Natl Acad Sci U S A 95: 10224-10228. doi:10.1073/pnas.95.17.10224. PubMed: 9707628.
[58]  Nogueira SV, Fonseca FL, Rodrigues ML, Mundodi V, Abi-Chacra EA et al. (2010) Paracoccidioides brasiliensis enolase is a surface protein that binds plasminogen and mediates interaction of yeast forms with host cells. Infect Immun 78: 4040-4050. doi:10.1128/IAI.00221-10. PubMed: 20605975.
[59]  López-Villar E, Monteoliva L, Larsen MR, Sachon E, Shabaz M et al. (2006) Genetic and proteomic evidences support the localization of yeast enolase in the cell surface. Proteomics 6 Suppl 1: S107-S118. doi:10.1002/pmic.200500479. PubMed: 16544286.
[60]  Pancholi V (2001) Multifunctional alpha-enolase: its role in diseases. Cell Mol Life Sci 58: 902-920. doi:10.1007/PL00000910. PubMed: 11497239.
[61]  Toledo A, Coleman JL, Kuhlow CJ, Crowley JT, Benach JL (2012) The enolase of Borrelia burgdorferi is a plasminogen receptor released in outer membrane vesicles. Infect Immun 80: 359-368. doi:10.1128/IAI.05836-11. PubMed: 22083700.
[62]  Stie J, Bruni G, Fox D (2009) Surface-associated plasminogen binding of Cryptococcus neoformans promotes extracellular matrix invasion. PLOS ONE 4: e5780. doi:10.1371/journal.pone.0005780. PubMed: 19492051.
[63]  Velineni S, Asuthkar S, Sritharan M (2006) Iron limitation and expression of immunoreactive outer membrane proteins in Leptospira interrogans serovar icterohaemorrhagiae strain Lai. Indian J Med Microbiol 24: 339-342. doi:10.4103/0255-0857.29414. PubMed: 17185872.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133