title: Characterization of Clostridium perfringens TpeL toxin gene carriage, production, cytotoxic contributions, and trypsin sensitivity.
abstract: Large clostridial toxins (LCTs) are produced by at least four pathogenic clostridial species, and several LCTs are proven pivotal virulence factors for both human and veterinary diseases. TpeL is a recently identified LCT produced by Clostridium perfringens that has received relatively limited study. In response, the current study surveyed carriage of the tpeL gene among different C. perfringens strains, detecting this toxin gene in some type A, B, and C strains but not in any type D or E strains. This study also determined that all tested strains maximally produce, and extracellularly release, TpeL at the late-log or early-stationary growth stage during in vitro culture, which is different from the maximal late-stationary-phase production reported previously for other LCTs and for TpeL production by C. perfringens strain JIR12688. In addition, the present study found that TpeL levels in culture supernatants can be repressed by either glucose or sucrose. It was also shown that, at natural production levels, TpeL is a significant contributor to the cytotoxic activity of supernatants from cultures of tpeL-positive strain CN3685. Lastly, this study identified TpeL, which presumably is produced in the intestines during diseases caused by TpeL-positive type B and C strains, as a toxin whose cytotoxicity decreases after treatment with trypsin; this finding may have pathophysiologic relevance by suggesting that, like beta toxin, TpeL contributes to type B and C infections in hosts with decreased trypsin levels due to disease, diet, or age.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA bamcc@pitt.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: McClane
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003016:Clostridium perfringens / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D013395:Sucrose / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism*; D014709:Vero Cells
chemical_list: D001427:Bacterial Toxins; D013395:Sucrose; D014357:Trypsin; D005947:Glucose
references.citation: Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6431-6
references.pmid: 24737893
references.citation: Microbiol Mol Biol Rev. 2013 Jun;77(2):208-33
references.pmid: 23699255
references.citation: Mol Microbiol. 1998 Jan;27(1):107-20
references.pmid: 9466260
references.citation: Infect Immun. 2006 Sep;74(9):5200-10
references.pmid: 16926413
references.citation: Anaerobe. 2010 Jun;16(3):314-5
references.pmid: 19961943
references.citation: J Infect Dis. 2006 Apr 15;193(8):1143-50
references.pmid: 16544255
references.citation: Anaerobe. 2012 Oct;18(5):546-52
references.pmid: 22982043
references.citation: Mol Microbiol. 2011 Feb;79(4):882-99
references.pmid: 21299645
references.citation: Infect Immun. 1992 Jan;60(1):102-10
references.pmid: 1729175
references.citation: Infect Immun. 2010 Nov;78(11):4860-9
references.pmid: 20823204
references.citation: Toxicon. 2013 Dec 1;75:136-43
references.pmid: 23851225
references.citation: Infect Immun. 2007 May;75(5):2391-8
references.pmid: 17339362
references.citation: Infect Immun. 2009 Dec;77(12):5291-9
references.pmid: 19805537
references.citation: MBio. 2013;4(5):e00770-13
references.pmid: 24105766
references.citation: Infect Immun. 1978 Aug;21(2):678-80
references.pmid: 211090
references.citation: Trends Microbiol. 2012 Jan;20(1):21-9
references.pmid: 22154163
references.citation: Infect Immun. 2010 Jan;78(1):495-504
references.pmid: 19858300
references.citation: Mol Microbiol. 2008 Jan;67(1):15-30
references.pmid: 18078439
references.citation: MBio. 2014;5(5):e01994-14
references.pmid: 25336460
references.citation: Infect Immun. 2005 Nov;73(11):7413-21
references.pmid: 16239541
references.citation: Anaerobe. 2005 Oct;11(5):262-72
references.pmid: 16701582
references.citation: Biochim Biophys Acta. 2004 Jul 6;1673(1-2):66-74
references.pmid: 15238250
references.citation: Future Microbiol. 2009 Oct;4(8):1021-64
references.pmid: 19824793
references.citation: Infect Immun. 2014 Nov;82(11):4620-30
references.pmid: 25135687
references.citation: Int J Med Microbiol. 2014 Nov;304(8):1147-59
references.pmid: 25190355
references.citation: Infect Immun. 1998 Sep;66(9):4531-6
references.pmid: 9712814
references.citation: PLoS One. 2011;6(5):e20376
references.pmid: 21655254
references.citation: Mol Microbiol. 2005 May;56(3):747-62
references.pmid: 15819629
references.citation: RNA. 2006 Jul;12(7):1271-81
references.pmid: 16741231
references.citation: Infect Immun. 2007 Apr;75(4):1811-9
references.pmid: 17261608
references.citation: Microb Pathog. 2012 Jan;52(1):85-91
references.pmid: 22079896
references.citation: Clin Microbiol Rev. 2005 Apr;18(2):247-63
references.pmid: 15831824
references.citation: J Bacteriol. 2008 Nov;190(21):7178-88
references.pmid: 18776010
references.citation: Appl Environ Microbiol. 2005 Nov;71(11):7542-7
references.pmid: 16269799
references.citation: Microbiol Immunol. 1988;32(6):551-64
references.pmid: 3173147
references.citation: Anaerobe. 2012 Feb;18(1):117-21
references.pmid: 22019986
references.citation: Infect Immun. 2014 Jul;82(7):2958-70
references.pmid: 24778117
references.citation: Annu Rev Microbiol. 1998;52:333-60
references.pmid: 9891801
references.citation: Infect Immun. 2007 Mar;75(3):1443-52
references.pmid: 17210666
references.citation: Mol Microbiol. 2007 Oct;66(1):206-19
references.pmid: 17725558
references.citation: Gene. 1997 Dec 5;203(1):65-73
references.pmid: 9426008
references.citation: J Biol Chem. 2012 Jul 20;287(30):24929-40
references.pmid: 22665487
references.citation: Infect Immun. 1983 Jun;40(3):943-9
references.pmid: 6303961
references.citation: Trends Microbiol. 2008 May;16(5):222-9
references.pmid: 18394902
references.citation: Appl Environ Microbiol. 1981 May;41(5):1184-91
references.pmid: 6266336
references.citation: Infect Immun. 2008 Oct;76(10):4396-404
references.pmid: 18625730
references.citation: Infect Immun. 2011 Feb;79(2):905-10
references.pmid: 21098103
references.citation: Anaerobe. 2006 Feb;12(1):23-43
references.pmid: 16701609
references.citation: Microbiol Immunol. 1997;41(7):527-35
references.pmid: 9272698
references.citation: Curr Top Microbiol Immunol. 2000;250:55-83
references.pmid: 10981357
references.citation: FEBS J. 2011 Dec;278(23):4589-601
references.pmid: 21518257
references.citation: MBio. 2011;2(6). pii: e00275-11. doi: 10.1128/mBio.00275-11
references.pmid: 22167225
references.citation: Toxins (Basel). 2010 Jul;2(7):1913-27
references.pmid: 22069665
references.citation: Microbiology. 2007 Apr;153(Pt 4):1198-206
references.pmid: 17379729
references.citation: PLoS One. 2011;6(7):e22053
references.pmid: 21814565
references.citation: Trends Microbiol. 1999 Mar;7(3):104-10
references.pmid: 10203838
references.citation: Infect Immun. 2000 Jul;68(7):3848-53
references.pmid: 10858193
references.citation: Infect Immun. 2012 Sep;80(9):3008-17
references.pmid: 22689820
references.citation: Gut Microbes. 2014 Jan-Feb;5(1):96-107
references.pmid: 24061146