Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Variations in the Antivirulence Effects of Fatty Acids and Virstatin against Vibrio cholerae Strains

  • Donghyun Lee (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Jayun Joo (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Hunseok Choi (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Seonghyeon Son (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Jonghyun Bae (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Dong Wook Kim (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Eun Jin Kim (Department of Pharmacy, College of Pharmacy, Hanyang University)
  • Received : 2024.05.07
  • Accepted : 2024.06.28
  • Published : 2024.09.28
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Abstract

The expression of two major virulence factors of Vibrio cholerae, cholera toxin (CT) and toxin co-regulated pilus (TCP), is induced by environmental stimuli through a cascade of interactions among regulatory proteins known as the ToxR regulon when the bacteria reach the human small intestine. ToxT is produced via the ToxR regulon and acts as the direct transcriptional activator of CT (ctxAB), TCP (tcp gene cluster), and other virulence genes. Unsaturated fatty acids (UFAs) and several small-molecule inhibitors of ToxT have been developed as antivirulence agents against V. cholerae. This study reports the inhibitory effects of fatty acids and virstatin (a small-molecule inhibitor of ToxT) on the transcriptional activation functions of ToxT in isogenic derivatives of V. cholerae strains containing various toxT alleles. The fatty acids and virstatin had discrete effects depending on the ToxT allele (different by 2 amino acids), V. cholerae strain, and culture conditions, indicating that V. cholerae strains could overcome the effects of UFAs and small-molecule inhibitors by acquiring point mutations in toxT. Our results suggest that small-molecule inhibitors should be examined thoroughly against various V. cholerae strains and toxT alleles during development.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)(RS-2023-00217123). DWK was supported by NRF-2021R1A2C1010857, and EJK was supported by NRF-RS-2023-00208573 from the NRF of Korea.

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