Dual-function regulator MexL as a target to control phenazines production and pathogenesis of Pseudomonas aeruginosa
Antibiotic resistance or tolerance of pathogens has become one of the global public crises. Finding new drug targets may open up a way of infection control. Phenazine pyocyanin (PYO) is an important virulence factor produced by the pathogen Pseudomonas aeruginosa. Here we show that a multidrug efflux pump repressor, MexL, acts as a transcriptional activator to enhance phenazines production via binding with a conserved DNA motif within the promoters of phenazines biosynthesis genes. Moreover, PYO functions as a self-regulating ligand of MexL for restricting its own production and the mexL knockout attenuates the virulence and antibiotics tolerance of P. aeruginosa. Based on the structure of MexL we resolve, we find two antimicrobials that can interact with MexL to reduce the PYO production and virulence of P. aeruginosa. Our in vivo studies suggest that the antimicrobials combination by using MexL-antagonists to reduce bacterial virulence and enhance the efficacy of common antibiotics can be an effective way to combat P. aeruginosa infection.
Authors
- Shumin Liao
- Yaqian Zheng (ORCID: https://orcid.org/0000-0002-5940-6756)
- Di Wang (ORCID: https://orcid.org/0000-0002-9103-4550)
- H. B. Liu (ORCID: https://orcid.org/0009-0000-6280-9962)
- Feng Long (ORCID: https://orcid.org/0000-0001-6313-8558)
- Zhikun Wu (ORCID: https://orcid.org/0000-0002-4583-7782)
- Zhenyu Zhang
- Liang Li (ORCID: https://orcid.org/0000-0003-1001-7837)
- Yu Zhang (ORCID: https://orcid.org/0000-0002-1778-8389)
- Xi Liu (ORCID: https://orcid.org/0000-0002-1901-1506)
- Z. Luyan (ORCID: https://orcid.org/0000-0002-3837-6682)
- Dejian Liu (ORCID: https://orcid.org/0000-0001-5019-7604)
- Yu Wei (ORCID: https://orcid.org/0000-0002-4432-7190)
- Yanhong Huang (ORCID: https://orcid.org/0000-0003-2102-4303)
- Haiying Yu
- Zhaoxiao Yu
- Wei Huang
Institutions
- Chinese Academy of Sciences (CN)
- Hubei University of Chinese Medicine (CN)
- Southern University of Science and Technology (CN)
- Wuhan University (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Microbiology Institute of Shaanxi (CN)
- Institute of Software (CN)
- Institute of Microbiology (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-26
- DOI
- https://doi.org/10.1038/s41467-025-57294-8
- Citations
- 9
- Primary Topic
- Bacterial biofilms and quorum sensing
- Type
- article
- Field-Weighted Citation Impact
- 7.25