Carvacrol and trans-cinnamaldehyde reduce Clostridium difficile toxin production and cytotoxicity in vitro

Shankumar Mooyottu, Anup Kollanoor-Johny, Genevieve Flock, Laurent Bouillaut, Abhinav Upadhyay, Abraham L. Sonenshein, Kumar Venkitanarayanan

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Clostridium difficile is a nosocomial pathogen that causes a serious toxin-mediated enteric disease in humans. Reducing C. difficile toxin production could significantly minimize its pathogenicity and improve disease outcomes in humans. This study investigated the efficacy of two, food-grade, plant-derived compounds, namely trans-cinnamaldehyde (TC) and carvacrol (CR) in reducing C. difficile toxin production and cytotoxicity in vitro. Three hypervirulent C. difficile isolates were grown with or without the sub-inhibitory concentrations of TC or CR, and the culture supernatant and the bacterial pellet were collected for total toxin quantitation, Vero cell cytotoxicity assay and RT-qPCR analysis of toxin-encoding genes. The effect of CR and TC on a codY mutant and wild type C. difficile was also investigated. Carvacrol and TC substantially reduced C. difficile toxin production and cytotoxicity on Vero cells. The plant compounds also significantly down-regulated toxin production genes. Carvacrol and TC did not inhibit toxin production in the codY mutant of C. difficile, suggesting a potential codY-mediated anti-toxigenic mechanism of the plant compounds. The antitoxigenic concentrations of CR and TC did not inhibit the growth of beneficial gut bacteria. Our results suggest that CR and TC could potentially be used to control C. difficile, and warrant future studies in vivo.

Original languageEnglish (US)
Pages (from-to)4415-4430
Number of pages16
JournalInternational journal of molecular sciences
Volume15
Issue number3
DOIs
StatePublished - Mar 12 2014
Externally publishedYes

Keywords

  • Clostridium difficile
  • Gene expression
  • Plant compounds
  • Toxins

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