The agr-like quorum-sensing system is important for clostridium perfringens type A strain ATCC 3624 To cause gas gangrene in a mouse model

Mauricio A. Navarro, Jihong Li, Juliann Beingesser, Bruce A. Mcclane, Francisco A. Uzal

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Clostridium perfringens type A is involved in gas gangrene in humans and animals. Following a traumatic injury, rapid bacterial proliferation and exotoxin production result in severe myonecrosis. C. perfringens alpha toxin (CPA) and perfringolysin (PFO) are the main virulence factors responsible for the disease. Recent in vitro studies have identified an Agr-like quorum-sensing (QS) system in C. perfringens that regulates the production of both toxins. The system is composed of an AgrB membrane transporter and an AgrD peptide that interacts with a two-component regulatory system in response to fluctuations in the cell population density. In addition, a synthetic peptide named 6-R has been shown to interfere with this signaling mechanism, affecting the function of the Agr-like QS system in vitro. In the present study, C. perfringens type A strain ATCC 3624 and an isogenic agrB-null mutant were tested in a mouse model of gas gangrene. When mice were intramuscularly challenged with 106 CFU of wild-type ATCC 3624, severe myonecrosis and leukocyte aggregation occurred by 4 h. Similar numbers of an agrB-null mutant strain produced significantly less severe changes in the skeletal muscle of challenged mice. Complementation of the mutant to regain agrB expression restored virulence to wild-type levels. The burdens of all three C. perfringens strains in infected muscle were similar. In addition, animals injected intramuscularly with wild-type ATCC 3624 coincubated with the 6-R peptide developed less severe microscopic changes. This study provides the first in vivo evidence that the Agr-like QS system is important for C. perfringens type A-mediated gas gangrene.

Original languageEnglish (US)
Article numbere00500
JournalmSphere
Volume5
Issue number3
DOIs
StatePublished - May 1 2020

Keywords

  • Agr-like quorum-sensing system
  • Clostridium perfringens
  • Gas gangrene

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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