This Article Full Text (PDF) Other Versions of this Article: AAC.01316-07v1 52/3/895    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rafii, F. Articles by Wagner, R. D. Search for Related Content PubMed PubMed Citation Articles by Rafii, F. Articles by Wagner, R. D.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.01316-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Enhanced production of phospholipase C and perfringolysin O (alpha and theta toxins) in a gatifloxacin-resistant strain of Clostridium perfringens

National Center for Toxicological Research, U.S. FDA, Jefferson, AR, Veterans Affairs Medical Center, Boise, ID, University of Washington School of Medicine, Seattle, WA

^* To whom correspondence should be addressed. Email: Fatemeh.Rafii{at}fda.hhs.gov.

	Abstract

Clostridium perfringens-induced gas gangrene is mediated by potent extracellular toxins, especially alpha toxin (a phospholipase C, PLC) and theta toxin (a thiol-activated cytolysin, perfringolysin O, PFO), and antibiotic-induced suppression of toxin synthesis is an important clinical goal. Production of PLC and PFO by a gatifloxacin-induced, fluoroquinolone-resistant mutant strain of C. perfringens Cp10G carrying a stable mutation in DNA gyrase was compared with that of the wild-type parent strain CpWT. Zymography (with sheep red blood cell and egg yolk overlays) and time-course analysis (with hydrolysis of egg-yolk lecithin and O-(4 nitrophenyl-phosphoryl)choline) demonstrated that Cp10G produced more PLC and PFO than CpWT. Increased toxin production in Cp10G was not related either to differences in growth characteristics between the wild type and the mutant strain or to non-synonymous polymorphisms in PLC, PFO or their known regulatory proteins. Increased PLC and PFO production by Cp10G was associated with increased cytotoxic activity for HT-29 human adenocarcinoma cells and with increased platelet/neutrophil aggregate formation. Four other gatifloxacin-induced gyrase mutants did not show increased toxin production, suggesting that gatifloxacin resistance was not always associated with increased toxin production in all strains of C. perfringens. This is the first report of increased toxin production in a fluoroquinolone-resistant strain of C. perfringens.