ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
This article is part of the Research TopicBiophysics and Molecular Biology of Antimicrobial Resistance: Toward New Targets and StrategiesView all 4 articles
MexS mediated heteroresistance of Pseudomonas aeruginosa to ciprofloxacin
Provisionally accepted
- 1Department of Biochemistry and Molecular Biology, Bengbu Medical University, Bengbu, China
- 2Department of Pediatrics, Department of Life Sciences and Medicine,University of Science and Technology of China, Hefei, China
- 3Department of Infectious Diseases, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
- 4Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 5Department of Microbiology, Bengbu Medical University, Bengbu, China
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Bacterial heteroresistance has been increasingly identified as an important phenomenon for many antibiotic/bacterium combinations. However the mechanisms underlying ciprofloxacin heteroresistance in P. aeruginosa, a key drug for treating this pathogen, remain poorly understood. In this study, 11 ciprofloxacin-heteroresistant P. aeruginosa isolates were identified by screening 226 clinical strains. Whole-genome sequencing (WGS) identified recurrent mutations within the mexS gene among these isolates. Crucially, CRISPR-Cas9-mediated deletion of mexS in the representative heteroresistant isolate (7318HR) abolished the heteroresistance phenotype, thereby confirming its functional necessity. Transcriptomic profiling following mexS deletion identified 532 differentially expressed genes involved in multiple biological processes, including phenazine biosynthesis, propanoate metabolism, bacterial secretion systems, and quorum sensing. Notably, genes associated with type IVb-tad pili were significantly downregulated. Consistent with this, the mexS mutant exhibited concurrent impairments in virulence-associated traits, including markedly reduced twitching motility (by approximately 38%) and polystyrene adhesion capacity (by approximately 50%) compared to the wild-type strain. These findings demonstrate that mexS is a key genetic determinant of ciprofloxacin heteroresistance in P. aeruginosa and concurrently modulates pilus-mediated virulence-associated functions.
Keywords: ciprofloxacin heteroresistance, mexS, P. aeruginosa, pilus-mediated virulence-associated functions, Twitching
Received: 05 Dec 2025; Accepted: 29 Jan 2026.
Copyright: © 2026 Ma, Chen, Chenlu, Li, Han, Li and Ni. 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:
Chengxi Li
Jinjing Ni
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