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Potent Bile Acid Microbial Metabolites Modulate Clostridium perfringens Virulence
Tahrir Alenezi1,2,3, Ying Fu1, Bilal Alrubaye1
1Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA.
Abstract:
Clostridium perfringens is a versatile pathogen, inducing diseases in the skin, intestine (such as chicken necrotic enteritis (NE)), and other organs. The classical sign of NE is the foul smell gas in the ballooned small intestine. We hypothesized that deoxycholic acid (DCA) reduced NE by inhibiting C. perfringens virulence signaling pathways. To evaluate the hypothesis, C. perfringens strains CP1 and wild-type (WT) HN13 and its mutants were cultured with different bile acids, including DCA and isoallolithocholic acid (isoalloLCA). Growth, hydrogen sulfide (H2S) production, and virulence gene expression were measured. Notably, isoalloLCA was more potent in reducing growth, H2S production, and virulence gene expression in CP1 and WT HN13 compared to DCA, while other bile acids were less potent compared to DCA. Interestingly, there was a slightly different impact between DCA and isoalloLCA on the growth, H2S production, and virulence gene expression in the three HN13 mutants, suggesting possibly different signaling pathways modulated by the two bile acids. In conclusion, DCA and isoalloLCA reduced C. perfringens virulence by transcriptionally modulating the pathogen signaling pathways. The findings could be used to design new strategies to prevent and treat C. perfringens-induced diseases.
Insights
Deoxycholic acid (DCA) and isoallolithocholic acid (isoalloLCA) reduce Clostridium perfringens virulence. These bile acids inhibit pathogen growth, hydrogen sulfide production, and virulence gene expression, offering new strategies against necrotic enteritis.
Area of Science:
- Microbiology
- Pathogen Signaling
- Bile Acid Research
Background:
- Clostridium perfringens causes various diseases, including necrotic enteritis (NE) in chickens, characterized by gas in the intestines.
- Virulence of C. perfringens is regulated by complex signaling pathways.
- Bile acids, such as deoxycholic acid (DCA), are investigated for their potential role in modulating pathogen virulence.
Purpose of the Study:
- To test the hypothesis that deoxycholic acid (DCA) inhibits Clostridium perfringens virulence signaling pathways, thereby reducing necrotic enteritis (NE).
- To compare the efficacy of DCA and isoallolithocholic acid (isoalloLCA) against C. perfringens growth, hydrogen sulfide (H2S) production, and virulence gene expression.
Main Methods:
- C. perfringens strains (CP1, WT HN13, and mutants) were cultured with various bile acids, including DCA and isoalloLCA.
- Measurements included bacterial growth, hydrogen sulfide (H2S) production, and expression of virulence genes.
- Comparative analysis was performed between DCA and isoalloLCA effects on wild-type and mutant strains.
Main Results:
- Isoallolithocholic acid (isoalloLCA) demonstrated greater potency than DCA in reducing C. perfringens growth, H2S production, and virulence gene expression.
- Both DCA and isoalloLCA transcriptionally modulated C. perfringens signaling pathways.
- Differential effects of DCA and isoalloLCA on bacterial mutants suggested distinct signaling pathway modulation.
Conclusions:
- Deoxycholic acid (DCA) and isoallolithocholic acid (isoalloLCA) effectively reduce Clostridium perfringens virulence.
- These bile acids act by transcriptionally modulating pathogen signaling pathways.
- The findings provide a basis for developing novel strategies to prevent and treat C. perfringens-associated diseases.
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