Host cell-induced signaling causes Clostridium perfringens to upregulate production of toxins important for intestinal infections

Abstract

Clostridium perfringens causes enteritis and enterotoxemia in humans and livestock due to prolific toxin production. In broth culture, C. perfringens uses the Agr-like quorum sensing (QS) system to regulate production of toxins important for enteritis/enterotoxemia, including beta toxin (CPB), enterotoxin, and epsilon toxin (ETX). The VirS/VirR two-component regulatory system (TCRS) also controls CPB production in broth cultures. Both the Agr-like QS and VirS/VirR systems are important when C. perfringens senses enterocyte-like Caco-2 cells and responds by upregulating CPB production; however, only the Agr-like QS system is needed for host cell-induced ETX production. These in vitro observations have pathophysiologic relevance since both the VirS/VirR and Agr-like QS signaling systems are required for C. perfringens strain CN3685 to produce CPB in vivo and to cause enteritis or enterotoxemia. Thus, apparently upon sensing its presence in the intestines, C. perfringens utilizes QS and TCRS signaling to produce toxins necessary for intestinal virulence.

Keywords: :

• Clostridium perfringens
• enterotoxin
• beta toxin
• epsilon toxin
• quorum sensing
• Agr
• two component regulatory system
• VirS/VirR
• intestinal infection

10.4161/gmic.26419

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Acknowledgments

Most of the research described in this review was generously supported by US Public Health Service Grants R37AI19844, R01AI056177–09, and a project in MARCE Grant 2U54AI57168–09 (M Levine, overall PI).