The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Food Microbiology
Volume 15 - 2024 |
doi: 10.3389/fmicb.2024.1468567
Identification and characterization of a small molecule BFstatin inhibiting BrpR, the transcriptional regulator for biofilm formation of Vibrio vulnificus
Provisionally accepted- 1 Seoul National University, Seoul, Republic of Korea
- 2 East China University of Science and Technology, Shanghai, Shanghai, China
Many pathogenic bacteria form biofilms that are resistant to not only host immune defenses but also antibiotics, posing a need for the development of strategies to control biofilms. In this study, to prevent biofilm formation of the fulminating foodborne pathogen Vibrio vulnificus, chemical libraries were extensively screened to identify a small molecule inhibiting the activity of BrpR, a transcriptional regulator for biofilm genes. Accordingly, the BrpR inhibitor BFstatin [N1-(2-chloro-5-fluorophenyl)-N3-propylmalonamide], with a half-maximal effective concentration of 8.01 μM, was identified. BFstatin did not interfere with bacterial growth or exhibit cytotoxicity to the human epithelial cell line. BFstatin directly bound to BrpR and interrupted its binding to the target promoter DNAs of the downstream genes. Molecular dynamics simulation of the interaction between BFstatin and BrpR proposed that BFstatin modifies the structure of BrpR, especially the DNA-binding domain. Transcriptomic analyses revealed that BFstatin reduces the expression of the BrpR regulon including the cabABC operon and brp locus which contribute to the production of biofilm matrix of V. vulnificus. Accordingly, BFstatin diminished the biofilm levels of V. vulnificus by inhibiting the matrix development in a concentration-dependent manner. Altogether, BFstatin could be an antibiofilm agent targeting BrpR, thereby rendering V. vulnificus more susceptible to host immune defenses and antibiotics.
Keywords: Biofilm, inhibitor, transcriptional regulator, pathogen, Vibrio vulnificus
Received: 22 Jul 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Lee, Hwang, Shin, Ha, Wang and Choi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sang Ho Choi, Seoul National University, Seoul, Republic of Korea
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.