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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Biofilms
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1424038
This article is part of the Research Topic Fighting Microbial Biofilms: Novel Therapeutics and Antibiofilm Strategies View all 5 articles

Two cinnamoyl hydroxamates as potential quorum sensing inhibitors against Pseudomonas aeruginosa

Provisionally accepted
Deng Pan Deng Pan 1Hua Wu Hua Wu 2Jun-Jian Li Jun-Jian Li 1Bo Wang Bo Wang 2Ai-Qun Jia Ai-Qun Jia 1*
  • 1 Hainan University, Haikou, Hainan Province, China
  • 2 Hainan General Hospital, Haikou, Hainan Province, China

The final, formatted version of the article will be published soon.

    Pseudomonas aeruginosa is a ubiquitous pathogen that causes various infectious diseases through the regulation of quorum sensing (QS). The strategy of interfering with the QS systems of P. aeruginosa, coupled with a reduction in the dosage of conventional antibiotics, presents a potential solution to treating infection and mitigating antibiotic resistance. In this study, seven cinnamoyl hydroxamates were synthesized to evaluate their inhibitory effects on QS of P. aeruginosa. Among these cinnamic acid derivatives, cinnamoyl hydroxamic acid (CHA) and 3-methoxycinnamoyl hydroxamic acid (MCHA) were the two most effective candidates. At subminimum inhibitory concentrations (sub-MICs), CHA and MCHA exhibited concentration-dependent attenuation of several QS-regulated virulence factors in P. aeruginosa. Notably, CHA and MCHA exerted significant inhibitory effects on pyocyanin production. Furthermore, a reduction in the swimming and swarming motilities of P. aeruginosa was observed after CHA and MCHA treatment. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) revealed that CHA (200 μg/mL) inhibited the expression of the rhlI, lasA, lasB, rhlA, rhlB, and oprL genes in P. aeruginosa by more than 80%, while MCHA (300 μg/mL) achieved similar inhibitory rates for rhlR, lasB, rhlA, and rhlB. Molecular docking indicated that CHA and MCHA primarily inhibited the RhlI/R system in P. aeruginosa by competing with the cognate signaling molecule C4-HSL, as verified by RT-qPCR. Additionally, CHA alone demonstrated a moderate disruptive effect on formed biofilms of P. aeruginosa, but when combined with gentamicin exhibited potent biofilm inhibitory activity, 3 suggesting that CHA can partially restore the susceptibility of P. aeruginosa to gentamicin by targeting biofilms.

    Keywords: cinnamoyl hydroxamates, Pseudomonas aeruginosa, Quorum sensing inhibitors, Biofilms, Gentamicin

    Received: 27 Apr 2024; Accepted: 18 Jul 2024.

    Copyright: © 2024 Pan, Wu, Li, Wang and Jia. 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: Ai-Qun Jia, Hainan University, Haikou, 570228, Hainan Province, China

    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.