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Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa
Abstract
Efflux pump systems are one of the most important mechanisms conferring multidrug resistance in Pseudomonas aeruginosa. MexAB-OprM efflux pump is one of the largest multi-drug resistant efflux pumps with high-level expression, which is controlled by regulatory genes mexR, nalC, and nalD. This study investigated the role of efflux pump MexAB-OprM in 75 strains of carbapenem-resistant P. aeruginosa and evaluated the influence of point mutation of the regulatory genes. The minimum inhibitory concentrations of imipenem and meropenem, with or without MC207110, an efflux pump inhibitor, were determined by agar dilution method to select the positive strains for an overexpressed active efflux pump. Carba NP test and EDTA-disk synergy test were used for the detection of carbapenemase and metallo-β-lactamases, respectively. The gene mexA, responsible for the fusion protein structure, and the reference gene rpoD of the MexAB-OprM pump were amplified by real-time PCR. The quantity of relative mRNA expression was determined simultaneously. By PCR method, the efflux regulatory genes mexR, nalC, and nalD and outer membrane protein OprD2 were amplified for the strains showing overexpression of MexAB-OprM and subsequently analyzed by BLAST. Among the 75 P. aeruginosa strains, the prevalence of efflux pump-positive phenotype was 17.3 % (13/75). Carba NP test and EDTA-disk synergy test were all negative in the 13 strains. PCR assay results showed that ten strains overexpressed the MexAB-OprM efflux pump and were all positive for the regulatory genes mexR, nalC, and nalD. Sequence analysis indicated that of the ten isolates, nine had a mutation (Gly → Glu) at 71st amino acid position in NalC, and eight also had a mutation (Ser → Arg) at 209th position in NalC. Only one strain had a mutation (Thr → Ile) at the 158th amino acid position in NalD, whereas eight isolates had mutations in MexR. In conclusion, overexpression of efflux pump MexAB-OprM plays an important role in carbapenem-resistant P. aeruginosa. The mutations of regulatory genes may be a main factor contributing to overexpression of MexAB-OprM.
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“Indeed, overexpression of the efflux pumps Cdr1, Cdr2, or Mdr1 is a common way adopted by C. albicans to detoxify itself from xenobiotics [100]; P. aeruginosa does the same with MexAB-OprM and MexXY-OprM [101], and S. enterica serovar Typhimurium increases the levels of AcrB to excrete β-lactam antibiotics [102].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [101]
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Cited by
Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
Caldara, M., & Marmiroli, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090915 · Cited by 54
Metadata
- Authors
- Pan, Y.-P., Xu, Y.-H., Wang, Z.-X., Fang, Y.-P., & Shen, J.-L.
- Affiliations
- Anhui Medical University (CN)
- Venue
- Archives of Microbiology
- Published
- 2016-04-08
- Volume
- 198
- Issue
- 6
- Pages
- 565-571
- ISSN
- 0003-9276 (ISSN-L)
- 0302-8933
- 1432-072X
- OpenAlex
- W2320908052
- Cited by
- 98
- References
- 30
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 13 · 2023: 15 · 2022: 9 · 2021: 15 · 2020: 8 · 2019: 10 · 2018: 5 · 2017: 2
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Archives of Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Fund Project (81171618)
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- carbapenem resistance, Pseudomonas aeruginosa, multidrug resistance, efflux pump overexpression, mexR, imipenem, meropenem, MexA
- MeSH terms
- Meropenem, Anti-Bacterial Agents, Bacterial Outer Membrane Proteins, Bacterial Proteins, beta-Lactamases, Genes, Regulator, Humans, Microbial Sensitivity Tests, Mutation, Phenotype, Pseudomonas aeruginosa, Repressor Proteins, Thienamycins, Carbapenems, Drug Resistance, Multiple, Bacterial, Membrane Transport Proteins, Real-Time Polymerase Chain Reaction
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- The paper
- Pan, Y.-P., Xu, Y.-H., Wang, Z.-X., Fang, Y.-P., & Shen, J.-L. (2016). Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa. Archives of Microbiology. https://doi.org/10.1007/s00203-016-1215-7
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
