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CodY Is a Global Regulator of Virulence-Associated Properties for Clostridium perfringens Type D Strain CN3718

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  • CodY is known to regulate various virulence properties in several Gram-positive bacteria but has not yet been studied in the important histotoxic and intestinal pathogen Clostridium perfringens. The present study prepared an isogenic codY-null mutant in C. perfringens type D strain CN3718 by insertional mutagenesis using the Targetron system. Western blot analysis indicated that, relative to wild-type CN3718 or a complementing strain, this isogenic codY mutant produces reduced levels of epsilon toxin (ETX). Using supernatants from cultures of the wild-type, codY-null mutant, and complementing strains, CodY regulation of ETX production was shown to have cytotoxic consequences for MDCK cells. The CodY regulatory effect on ETX production was specific, since the codY-null mutant still made wild-type levels of alpha-toxin and perfringolysin O. Sialidase activity measurements and sialidase Western blot analysis of supernatants from CN3718 and its isogenic derivatives showed that CodY represses overall exosialidase activity due to a reduced presence of NanH in culture supernatants. Inactivation of the codY gene significantly decreased the adherence of CN3718 vegetative cells or spores to host Caco-2 cells. Finally, the codY mutant showed increased spore formation under vegetative growth conditions, although germination of these spores was impaired. Overall, these results identify CodY as a global regulator of many C. perfringens virulence-associated properties. Furthermore, they establish that, via CodY, CN3718 coordinately regulates many virulence-associated properties likely needed for intestinal infection.
  • This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the American Society for Microbiology. The published article can be found at: http://mbio.asm.org/.
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  • Li J, Ma M, Sarker MR, McClane BA. 2013. CodY is a global regulator of virulence-associated properties for Clostridium perfringens type D strain CN3718. mBio 4(5):e00770-13. doi:10.1128/mBio.00770-13.
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  • 4
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  • 5
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  • This research was generously supported by U.S. Public Health Service grant R01AI056177-09 (B.A.M.), by a project grant to B.A.M. from the Middle Atlantic Regional Center of Excellence, grant 2U54AI57168-09, bygrant R03 AI105635-01 (J.L.), and by a Department of Defense Multidisciplinary University Research Initiative (MURI) award through theU.S. Army Research Laboratory and the U.S. Army Research Office under contract number W911NF-09-1-0286 (M.R.S.).
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