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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1562096
This article is part of the Research Topic Unveiling the Future of Antibiotics: Exploring the WHO Priority List of Antibiotic-Resistant Bacteria for Discovery, Research, and Development of Novel Therapeutics View all 4 articles
Chlorogenic Acid Inhibits Virulence and Resistance Gene Transfer in Outer Membrane Vesicles of Carbapenem-Resistant Klebsiella pneumoniae
Provisionally accepted- 1 Zhejiang Chinese Medical University, Hangzhou, China
- 2 First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
- 3 Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China
Carbapenem-resistant Klebsiella pneumoniae (CRKp) infection poses a significant global public health challenge, with the misuse of antibiotics further contributing to the development of resistance and triggering harmful inflammatory responses. Outer membrane vesicle (OMVs) released by CRKp under sub-lethal concentration of MEM pressure (KOMV-MEM) exhibit enhanced virulence and greater efficiency in transferring resistance genes. This study confirmed that the increased inflammation and bacterial load observed in CRKp-infected mice under MEM pressure were attributable to the high virulence of KOMV-MEM. We concurrently investigated the inhibitory effects of chlorogenic acid (CA) on KOMV-MEM characteristics and its protective role in KOMV-MEM infected mice. Based on LC-MS proteomic analysis of vesicles, we screened for potential targets of KOMV-MEM in promoting macrophage (MØ) pyroptosis pathways and inducing resistance gene transfer. Computational predictions and experimental validation revealed that CA inhibits pyroptosis by reducing MØ capture of KOMV-MEM via blocking the interaction between GroEL and LOX-1. Furthermore, CA was found to prevent the spread of resistance genes by disrupting the conjugation and transfer processes between KOMV-MEM and recipient bacteria. Finally, our in vitro and in vivo studies showed that CA can inhibit KOMV-MEM resistance enzymes, thereby preventing the hydrolysis of MEM in the environment and depriving susceptible bacteria of protection. In summary, these results provide the first confirmation that CA can inhibit the virulence and transmission of drug resistance in KOMV-MEM. This underscores that CA treatment for CRKp infection is a promising antimicrobial strategy.
Keywords: Outer membrane vesicle, carbapenem-resistant Klebsiella pneumoniae, Resistance gene transfer, Cell pyroptosis, Chlorogenic Acid
Received: 16 Jan 2025; Accepted: 07 Mar 2025.
Copyright: © 2025 Wang, Wan, Yu, Du, Zhou, Wan and Yang. 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:
Jiehong Yang, Zhejiang Chinese Medical University, Hangzhou, China
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