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Toxins  2010 

NetB, a Pore-Forming Toxin from Necrotic Enteritis Strains of Clostridium perfringens

DOI: 10.3390/toxins2071913

Keywords: NetB, necrotic enteritis, Clostridium perfringens, pore-forming toxin

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Abstract:

The Clostridium perfringens necrotic enteritis B-like toxin (NetB) is a recently discovered member of the β-barrel pore-forming toxin family and is produced by a subset of avian C. perfringens type A strains. NetB is cytotoxic for avian cells and is associated with avian necrotic enteritis. This review examines the current state of knowledge of NetB: its role in pathogenesis, its distribution and expression in C. perfringens and its vaccine?potential.

References

[1]  Hatheway, C.L. Toxigenic clostridia. Clin. Microbiol. Rev.?1990, 3, 66–98. 2404569
[2]  Petit, L.; Gibert, M.; Popoff, M.R. Clostridium perfringens: toxinotype and genotype. Trends Microbiol.?1999, 7, 104–110, doi:10.1016/S0966-842X(98)01430-9. 10203838
[3]  Rood, J.I. Virulence genes of Clostridium perfringens. Annu. Rev. Microbiol.?1998, 52, 333–360, doi:10.1146/annurev.micro.52.1.333. 9891801
[4]  Smedley, J.G., III; Fisher, D.J.; Sayeed, S.; Chakrabarti, G.; McClane, B.A. The enteric toxins of Clostridium perfringens. Rev. Physiol. Biochem. Pharmacol.?2004, 152, 183–204. 15517462
[5]  Songer, J.G. Clostridial enteric diseases of domestic animals. Clin. Microbiol. Rev.?1996, 9, 216–234. 8964036
[6]  Brynestad, S.; Granum, P.E. Clostridium perfringens and foodborne infections. Int. J. Food Microbiol.?2002, 74, 195–202, doi:10.1016/S0168-1605(01)00680-8. 11981970
[7]  Rood, J.I.; McClane, B.A. Clostridium perfringens: enterotoxaemic Diseases. In Molecular Medical Microbiology; Sussman, M., Ed.; Academic: London, UK, 2002; Volume 1, pp. 1117–1139.
[8]  Rood, J.I. Clostridium perfringens and histotoxic disease. In The Prokaryotes: A Handbook on the Biology of Bacteria, 3rd; Dworkin, M., Falkow, S., Rosenberg, E., Schleifer, K.H., Stackebrandt, E., Eds.; Springer: New York, NY, USA, 2007; Volume 4, pp. 753–770.
[9]  Van der Sluis, W. Clostridial enteritis—a syndrome. World Poultry?2000, 16, 56–57.
[10]  Van der Sluis, W. Clostridial enteritis is an often underestimated problem. World Poultry?2000, 16, 42–43.
[11]  Lovland, A.; Kaldhusdal, M. Severely impaired production performance in broiler flocks with high incidence of Clostridium perfringens-associated hepatitis. Avian Pathol.?2001, 30, 73–81, doi:10.1080/03079450020023230. 19184877
[12]  Kaldhusdal, M.; Hofshagen, M. Barley inclusion and avoparcin supplementation in broiler diets. 2. Clinical, pathological, and bacteriological findings in a mild form of necrotic enteritis. Poult. Sci.?1992, 71, 1145–1153. 1641378
[13]  Helmboldt, C.F.; Bryant, E.S. The pathology of necrotic enteritis in domestic fowl. Avian Dis.?1971, 15, 775–780, doi:10.2307/1588866. 5159549
[14]  Al-Sheikhly, F.; Truscott, R.B. The pathology of necrotic enteritis of chickens following infusion of broth cultures of Clostridium perfringens into the duodenum. Avian Dis.?1977, 21, 230–240, doi:10.2307/1589343. 194570
[15]  Al-Sheikhly, F.; Al-Saieg, A. Role of Coccidia in the occurrence of necrotic enteritis of chickens. Avian Dis.?1980, 24, 324–333, doi:10.2307/1589700. 6254485
[16]  Gazdzinski, P.; Julian, R.J. Necrotic enteritis in turkeys. Avian Dis.?1992, 36, 792–798, doi:10.2307/1591787. 1417616
[17]  Van Immerseel, F.; De Buck, J.; Pasmans, F.; Huyghebaert, G.; Haesebrouck, F.; Ducatelle, R. Clostridium perfringens in poultry: an emerging threat for animal and public health. Avian Pathol.?2004, 33, 537–549, doi:10.1080/03079450400013162. 15763720
[18]  Broussard, C.T.; Hofacre, C.L.; Page, R.K.; Fletcher, O.J. Necrotic enteritis in cage-reared commercial layer pullets. Avian Dis.?1986, 30, 617–619, doi:10.2307/1590433. 2876698
[19]  Awad, M.M.; Bryant, A.E.; Stevens, D.L.; Rood, J.I. Virulence studies on chromosomal alpha-toxin and theta-toxin mutants constructed by allelic exchange provide genetic evidence for the essential role of alpha-toxin in Clostridium perfringens-mediated gas gangrene. Mol. Microbiol.?1995, 15, 191–202, doi:10.1111/j.1365-2958.1995.tb02234.x. 7746141
[20]  Al-Sheikhly, F.; Truscott, R.B. The pathology of necrotic enteritis of chickens following infusion of crude toxins of Clostridium perfringens into the duodenum. Avian Dis.?1977, 21, 241–255, doi:10.2307/1589344. 194571
[21]  Fukata, T.; Hadate, Y.; Baba, E.; Uemura, T.; Arakawa, A. Influence of Clostridium perfringens and its toxin in germ-free chickens. Res. Vet. Sci.?1988, 44, 68–70. 2897708
[22]  Keyburn, A.L.; Sheedy, S.A.; Ford, M.E.; Williamson, M.M.; Awad, M.M.; Rood, J.I.; Moore, R.J. Alpha-toxin of Clostridium perfringens is not an essential virulence factor in necrotic enteritis in chickens. Infect. Immun.?2006, 74, 6496–6500, doi:10.1128/IAI.00806-06. 16923791
[23]  Keyburn, A.L.; Boyce, J.D.; Vaz, P.; Bannam, T.L.; Ford, M.E.; Parker, D.; Di Rubbo, A.; Rood, J.I.; Moore, R.J. NetB, a new toxin that is associated with avian necrotic enteritis caused by Clostridium perfringens. PLoS Pathog.?2008, 4, e26, doi:10.1371/journal.ppat.0040026. 18266469
[24]  Alouf, J.E. Pore-forming bacterial protein toxins: an overview. Curr. Top. Microbiol. Immunol.?2001, 257, 1–14. 11417117
[25]  Bhakdi, S.; Tranum-Jensen, J. Alpha-toxin of Staphylococcus aureus. Microbiol. Rev.?1991, 55, 733–751. 1779933
[26]  Paton, J.C. The contribution of pneumolysin to the pathogenicity of Streptococcus pneumoniae. Trends Microbiol.?1996, 4, 103–106, doi:10.1016/0966-842X(96)81526-5. 8868088
[27]  Rubins, J.B.; Charboneau, D.; Fasching, C.; Berry, A.M.; Paton, J.C.; Alexander, J.E.; Andrew, P.W.; Mitchell, T.J.; Janoff, E.N. Distinct roles for pneumolysin's cytotoxic and complement activities in the pathogenesis of pneumococcal pneumonia. Am. J. Respir. Crit. Care Med.?1996, 153, 1339–1346. 8616564
[28]  Ellemor, D.M.; Baird, R.N.; Awad, M.M.; Boyd, R.L.; Rood, J.I.; Emmins, J.J. Use of genetically manipulated strains of Clostridium perfringens reveals that both alpha-toxin and theta-toxin are required for vascular leukostasis to occur in experimental gas gangrene. Infect. Immun.?1999, 67, 4902–4907. 10456947
[29]  Schmiel, D.H.; Miller, V.L. Bacterial phospholipases and pathogenesis. Microbes Infect.?1999, 1, 1103–1112, doi:10.1016/S1286-4579(99)00205-1. 10572314
[30]  Titball, R.W. Membrane-damaging and cytotoxic phospholipases. In The Comprehensive Sourcebook of Bacterial Protein Toxins; Alouf, J.E., Freer, J.H., Eds.; Academic: London, UK, 1999; pp. 311–329.
[31]  Kennedy, C.L.; Krejany, E.O.; Young, L.F.; O'Connor, J.R.; Awad, M.M.; Boyd, R.L.; Emmins, J.J.; Lyras, D.; Rood, J.I. The alpha-toxin of Clostridium septicum is essential for virulence. Mol. Microbiol.?2005, 57, 1357–1366, doi:10.1111/j.1365-2958.2005.04774.x. 16102005
[32]  Prevost, G.; Mourey, L.; Colin, D.A.; Menestrina, G. Staphylococcal pore-forming toxins. Curr. Top. Microbiol. Immunol.?2001, 257, 53–83. 11417122
[33]  Gouaux, E. alpha-Hemolysin from Staphylococcus aureus: an archetype of beta-barrel, channel-forming toxins. J. Struct. Biol.?1998, 121, 110–122, doi:10.1006/jsbi.1998.3959. 9615434
[34]  Tweten, R.K.; Christianson, K.K.; Iandolo, J.J. Transport and processing of staphylococcal alpha-toxin. J. Bacteriol.?1983, 156, 524–528. 6630145
[35]  Gray, G.S.; Kehoe, M. Primary sequence of the alpha-toxin gene from Staphylococcus aureus wood 46. Infect. Immun.?1984, 46, 615–618. 6500704
[36]  Shatursky, O.; Bayles, R.; Rogers, M.; Jost, B.H.; Songer, J.G.; Tweten, R.K. Clostridium perfringens beta-toxin forms potential-dependent, cation-selective channels in lipid bilayers. Infect. Immun.?2000, 68, 5546–5551, doi:10.1128/IAI.68.10.5546-5551.2000. 10992452
[37]  Sakurai, J.; Duncan, C.L. Some properties of beta-toxin produced by Clostridium perfringens type C. Infect. Immun.?1978, 21, 678–680. 211090
[38]  Vidal, J.E.; McClane, B.A.; Saputo, J.; Parker, J.; Uzal, F.A. Effects of Clostridium perfringens beta-toxin on the rabbit small intestine and colon. Infect. Immun.?2008, 76, 4396–4404, doi:10.1128/IAI.00547-08. 18625730
[39]  Katayama, S.; Dupuy, B.; Daube, G.; China, B.; Cole, S.T. Genome mapping of Clostridium perfringens strains with I-CeuI shows many virulence genes to be plasmid-borne. Mol. Gen. Genet.?1996, 251, 720–726. 8757404
[40]  Hunter, S.E.; Brown, J.E.; Oyston, P.C.; Sakurai, J.; Titball, R.W. Molecular genetic analysis of beta-toxin of Clostridium perfringens reveals sequence homology with alpha-toxin, gamma-toxin, and leukocidin of Staphylococcus aureus. Infect. Immun.?1993, 61, 3958–3965. 8359918
[41]  Steinthorsdottir, V.; Fridriksdottir, V.; Gunnarsson, E.; Andresson, O.S. Site-directed mutagenesis of Clostridium perfringens beta-toxin: expression of wild-type and mutant toxins in Bacillus subtilis. FEMS Microbiol. Lett.?1998, 158, 17–23, doi:10.1111/j.1574-6968.1998.tb12794.x. 9453152
[42]  Nagahama, M.; Kihara, A.; Miyawaki, T.; Mukai, M.; Sakaguchi, Y.; Ochi, S.; Sakurai, J. Clostridium perfringens beta-toxin is sensitive to thiol-group modification but does not require a thiol group for lethal activity. Biochim. Biophys. Acta?1999, 1454, 97–105, doi:10.1016/S0925-4439(99)00026-5. 10354519
[43]  Walker, B.; Bayley, H. Key residues for membrane binding, oligomerization, and pore forming activity of staphylococcal alpha-hemolysin identified by cysteine scanning mutagenesis and targeted chemical modification. J. Biol. Chem.?1995, 270, 23065–23071, doi:10.1074/jbc.270.39.23065. 7559447
[44]  Song, L.; Hobaugh, M.R.; Shustak, C.; Cheley, S.; Bayley, H.; Gouaux, J.E. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science?1996, 274, 1859–1866, doi:10.1126/science.274.5294.1859. 8943190
[45]  Nagahama, M.; Hayashi, S.; Morimitsu, S.; Sakurai, J. Biological activities and pore formation of Clostridium perfringens beta toxin in HL 60 cells. J. Biol. Chem.?2003, 278, 36934–36941, doi:10.1074/jbc.M306562200. 12851396
[46]  Manich, M.; Knapp, O.; Gibert, M.; Maier, E.; Jolivet-Reynaud, C.; Geny, B.; Benz, R.; Popoff, M.R. Clostridium perfringens delta toxin is sequence related to beta toxin, NetB, and Staphylococcus pore-forming toxins, but shows functional differences. PLoS One?2008, 3, e3764, doi:10.1371/journal.pone.0003764. 19018299
[47]  Alouf, J.E.; Jolivet-Reynaud, C. Purification and characterization of Clostridium perfringens delta-toxin. Infect. Immun.?1981, 31, 536–546. 6260669
[48]  Jolivet-Reynaud, C.; Cavaillon, J.M.; Alouf, J.E. Selective cytotoxicity of Clostridium perfringens delta toxin on rabbit leukocytes. Infect. Immun.?1982, 38, 860–864. 6295950
[49]  Cavaillon, J.M.; Jolivet-Reynaud, C.; Fitting, C.; David, B.; Alouf, J.E. Ganglioside identification on human monocyte membrane with Clostridium perfringens delta-toxin. J. Leukoc. Biol.?1986, 40, 65–72. 2872258
[50]  Jolivet-Reynaud, C.; Launay, J.M.; Alouf, J.E. Damaging effects of Clostridium perfringens delta toxin on blood platelets and their relevance to ganglioside GM2. Arch. Biochem. Biophys.?1988, 262, 59–66, doi:10.1016/0003-9861(88)90168-3. 3162668
[51]  Patel, A.H.; Nowlan, P.; Weavers, E.D.; Foster, T. Virulence of protein A-deficient and alpha-toxin-deficient mutants of Staphylococcus aureus isolated by allele replacement. Infect. Immun.?1987, 55, 3103–3110. 3679545
[52]  Sayeed, S.; Uzal, F.A.; Fisher, D.J.; Saputo, J.; Vidal, J.E.; Chen, Y.; Gupta, P.; Rood, J.I.; McClane, B.A. Beta toxin is essential for the intestinal virulence of Clostridium perfringens type C disease isolate CN3685 in a rabbit ileal loop model. Mol. Microbiol.?2008, 67, 15–30. 18078439
[53]  Bergeland, M.E. Pathogenesis and immunity of Clostridium perfringens type C enteritis in swine. J. Am. Vet. Med. Assoc.?1972, 160, 568–571. 4337842
[54]  Fisher, D.J.; Fernandez-Miyakawa, M.E.; Sayeed, S.; Poon, R.; Adams, V.; Rood, J.I.; Uzal, F.A.; McClane, B.A. Dissecting the contributions of Clostridium perfringens type C toxins to lethality in the mouse intravenous injection model. Infect. Immun.?2006, 74, 5200–5210, doi:10.1128/IAI.00534-06. 16926413
[55]  Lepp, D.; Roxas, B.; Parreira, V.R.; Marri, P.R.; Rosey, E.L.; Gong, J.; Songer, J.G.; Vedantam, G.; Prescott, J.F. Identification of novel pathogenicity loci in Clostridium perfringens strains that cause avian necrotic enteritis. PLoS One?2010, 5, e10795, doi:10.1371/journal.pone.0010795. 20532244
[56]  Engstrom, B.E.; Fermer, C.; Lindberg, A.; Saarinen, E.; Baverud, V.; Gunnarsson, A. Molecular typing of isolates of Clostridium perfringens from healthy and diseased poultry. Vet. Microbiol.?2003, 94, 225–235, doi:10.1016/S0378-1135(03)00106-8. 12814890
[57]  Nauerby, B.; Pedersen, K.; Madsen, M. Analysis by pulsed-field gel electrophoresis of the genetic diversity among Clostridium perfringens isolates from chickens. Vet. Microbiol.?2003, 94, 257–266, doi:10.1016/S0378-1135(03)00118-4. 12814893
[58]  Gholamiandekhordi, A.R.; Ducatelle, R.; Heyndrickx, M.; Haesebrouck, F.; Van Immerseel, F. Molecular and phenotypical characterization of Clostridium perfringens isolates from poultry flocks with different disease status. Vet. Microbiol.?2006, 113, 143–152, doi:10.1016/j.vetmic.2005.10.023. 16337097
[59]  Chalmers, G.; Bruce, H.L.; Hunter, D.B.; Parreira, V.R.; Kulkarni, R.R.; Jiang, Y.F.; Prescott, J.F.; Boerlin, P. Multilocus sequence typing analysis of Clostridium perfringens isolates from necrotic enteritis outbreaks in broiler chicken populations. J. Clin. Microbiol.?2008, 46, 3957–3964, doi:10.1128/JCM.01548-08. 18945840
[60]  Chalmers, G.; Martin, S.W.; Hunter, D.B.; Prescott, J.F.; Weber, L.J.; Boerlin, P. Genetic diversity of Clostridium perfringens isolated from healthy broiler chickens at a commercial farm. Vet. Microbiol.?2008, 127, 116–127, doi:10.1016/j.vetmic.2007.08.008. 17888591
[61]  Chalmers, G.; Martin, S.W.; Prescott, J.F.; Boerlin, P. Typing of Clostridium perfringens by multiple-locus variable number of tandem repeats analysis. Vet. Microbiol.?2008, 128, 126–135, doi:10.1016/j.vetmic.2007.09.018. 18022331
[62]  Drigo, I.; Agnoletti, F.; Bacchin, C.; Bettini, F.; Cocchi, M.; Ferro, T.; Marcon, B.; Bano, L. Toxin genotyping of Clostridium perfringens field strains isolated from healthy and diseased chickens. Ital. J. Anim. Sci.?2008, 7, 397–400.
[63]  Timbermont, L.; Lanckriet, A.; Gholamiandehkordi, A.R.; Pasmans, F.; Martel, A.; Haesebrouck, F.; Ducatelle, R.; Van Immerseel, F. Origin of Clostridium perfringens isolates determines the ability to induce necrotic enteritis in broilers. Comp. Immunol. Microbiol. Infect. Dis.?2008, 32, 503–512. 18783830
[64]  Johansson, A.; Aspan, A.; Kaldhusdal, M.; Engstrom, B.E. Genetic diversity and prevalence of netB in Clostridium perfringens isolated from a broiler flock affected by mild necrotic enteritis. Vet. Microbiol.?2009, 144, 87–92. 20056357
[65]  Martin, T.G.; Smyth, J.A. Prevalence of netB among some clinical isolates of Clostridium perfringens from animals in the United States. Vet. Microbiol.?2009, 136, 202–205, doi:10.1016/j.vetmic.2008.10.026. 19081686
[66]  Keyburn, A.L.; Yan, X.X.; Bannam, T.L.; Van Immerseel, F.; Rood, J.I.; Moore, R.J. Association between avian necrotic enteritis and Clostridium perfringens strains expressing NetB toxin. Vet. Res.?2010, 41, 21, doi:10.1051/vetres/2009069. 19931005
[67]  Smyth, J.A.; Martin, T.G. Disease producing capability of netB positive isolates of C. perfringens recovered from normal chickens and a cow, and netB positive and negative isolates from chickens with necrotic enteritis. Vet. Microbiol.?2010.
[68]  Abildgaard, L.; Sondergaard, T.E.; Engberg, R.M.; Schramm, A.; Hojberg, O. In vitro production of necrotic enteritis toxin B, NetB, by netB-positive and netB-negative Clostridium perfringens originating from healthy and diseased broiler chickens. Vet. Microbiol.?2010, 144, 231–235, doi:10.1016/j.vetmic.2009.12.036. 20092968
[69]  Cooper, K.K.; Songer, J.G. Virulence of Clostridium perfringens in an experimental model of poultry necrotic enteritis. Vet. Microbiol.?2010, 142, 323–328, doi:10.1016/j.vetmic.2009.09.065. 19931323
[70]  Nowell, V.J.; Poppe, C.; Parreira, V.R.; Jiang, Y.F.; Reid-Smith, R.; Prescott, J.F. Clostridium perfringens in retail chicken. Anaerobe?2010, 16, 314–315, doi:10.1016/j.anaerobe.2009.11.004. 19961943
[71]  Cheung, J.K.; Keyburn, A.L.; Carter, G.P.; Lanckriet, A.L.; Van Immerseel, F.; Moore, R.J.; Rood, J.I. The VirSR two-component signal transduction system regulates NetB toxin production in Clostridium perfringens. Infect. Immun.?2010, 78, 3064–3072, doi:10.1128/IAI.00123-10. 20457789
[72]  Ohtani, K.; Hirakawa, H.; Tashiro, K.; Yoshizawa, S.; Kuhara, S.; Shimizu, T. Identification of a two-component VirR/VirS regulon in Clostridium perfringens. Anaerobe?2010, 16, 258–264, doi:10.1016/j.anaerobe.2009.10.003. 19835966
[73]  Ohtani, K.; Yuan, Y.; Hassan, S.; Wang, R.; Wang, Y.; Shimizu, T. Virulence gene regulation by the agr system in Clostridium perfringens. J. Bacteriol.?2009, 191, 3919–3927, doi:10.1128/JB.01455-08. 19363118
[74]  McDevitt, R.M.; Brooker, J.D.; Acamovic, T.; Sparks, N.H.C. Necrotic enteritis; a continuing challenge for the poultry industry. Worlds Poult. Sci. J.?2006, 62, 221–247, doi:10.1079/WPS200593.
[75]  Lawrence, G.W.; Lehmann, D.; Anian, G.; Coakley, C.A.; Saleu, G.; Barker, M.J.; Davis, M.W. Impact of active immunisation against enteritis necroticans in Papua New Guinea. Lancet?1990, 336, 1165–1167, doi:10.1016/0140-6736(90)92776-E. 1978034
[76]  Uzal, F.A.; Kelly, W.R. Protection of goats against experimental enterotoxaemia by vaccination with Clostridium perfringens type D epsilon toxoid. Vet. Rec.?1998, 142, 722–725, doi:10.1136/vr.142.26.722. 9682431
[77]  Springer, S.; Selbitz, H.J. The control of necrotic enteritis in sucking piglets by means of a Clostridium perfringens toxoid vaccine. FEMS Immunol. Med. Microbiol.?1999, 24, 333–336, doi:10.1111/j.1574-695X.1999.tb01302.x. 10397319
[78]  Heier, B.T.; Lovland, A.; Soleim, K.B.; Kaldhusdal, M.; Jarp, J. A field study of naturally occurring specific antibodies against Clostridium perfringens alpha toxin in Norwegian broiler flocks. Avian Dis.?2001, 45, 724–732, doi:10.2307/1592919. 11569751
[79]  Lovland, A.; Kaldhusdal, M.; Redhead, K.; Skjerve, E.; Lillehaug, A. Maternal vaccination against subclinical necrotic enteritis in broilers. Avian Pathol.?2004, 33, 83–92. 14681072
[80]  Kulkarni, R.R.; Parreira, V.R.; Sharif, S.; Prescott, J.F. Clostridium perfringens antigens recognized by broiler chickens immune to necrotic enteritis. Clin. Vaccine Immunol.?2006, 13, 1358–1362, doi:10.1128/CVI.00292-06. 17065258
[81]  Kulkarni, R.R.; Parreira, V.R.; Sharif, S.; Prescott, J.F. Immunization of broiler chickens against Clostridium perfringens-induced necrotic enteritis. Clin. Vaccine Immunol.?2007, 14, 1070–1077, doi:10.1128/CVI.00162-07. 17634510
[82]  Zekarias, B.; Mo, H.; Curtiss, R., III. Recombinant attenuated Salmonella enterica serovar typhimurium expressing the carboxy-terminal domain of alpha toxin from Clostridium perfringens induces protective responses against necrotic enteritis in chickens. Clin. Vaccine Immunol.?2008, 15, 805–816, doi:10.1128/CVI.00457-07. 18337376
[83]  Wardenburg, J.B.; Schneewind, O. Vaccine protection against Staphylococcus aureus pneumonia. J. Exp. Med.?2008, 205, 287–294, doi:10.1084/jem.20072208. 18268041
[84]  Ragle, B.E.; Wardenburg, J.B. Anti-alpha-hemolysin monoclonal antibodies mediate protection against Staphylococcus aureus pneumonia. Infect. Immun.?2009, 77, 2712–2718, doi:10.1128/IAI.00115-09. 19380475

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