Multidrug Efflux Pump AcrAB of Salmonella typhimurium Excretes Only Those β-Lactam Antibiotics Containing Lipophilic Side Chains
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We found that the previously reported SS-B drug-supersusceptible mutant of Salmonella typhimurium (S. Sukupolvi, M. Vaara, I. M. Helander, P. Viljanen, and P. H. Mäkelä, J. Bacteriol. 159:704–712, 1984) had a mutation in the acrAB operon. Comparison of this mutant with its parent strain and with an AcrAB-overproducing strain showed that the activity of the AcrAB efflux pump often produced significant resistance to β-lactam antibiotics in the complete absence of β-lactamase. The effect of AcrAB activity on resistance was more pronounced with agents containing more lipophilic side chains, suggesting that such compounds were better substrates for this pump. This correlation is consistent with the hypothesis that only those molecules that become at least partially partitioned into the lipid bilayer of the cytoplasmic membrane are captured by the AcrAB pump. According to this mechanism, the pump successfully excretes even those β-lactams that fail to traverse the cytoplasmic membrane, because these compounds are likely to become partitioned into the outer leaflet of the bilayer. Even the compounds with lipophilic side chains were shown to penetrate across the outer membrane relatively rapidly, if the pump was inactivated genetically or physiologically. The exclusion of such compounds, exemplified by nafcillin, from cells of the wild-type S. typhimurium was previously interpreted as the result of poor diffusion across the outer membrane (H. Nikaido, Biochim. Biophys. Acta 433:118–132, 1976), but it is now recognized as the consequence of efficient pumping out of entering antibiotics by the active efflux process.
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S. enterica serovar Typhimurium increases levels of AcrB to excrete β-lactam antibiotics.
“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 [102]
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- Authors
- Nikaido, H., Basina, M., Nguyen, V., & Rosenberg, E. Y.
- Affiliations
- University of California, Berkeley (US)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 1998-09
- Volume
- 180
- Issue
- 17
- Pages
- 4686-4692
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC107484
- OpenAlex
- W1909542718
- Cited by
- 224
- References
- 39
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 10 · 2015: 7 · 2014: 4 · 2013: 4 · 2012: 5
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R37AI009644, R01AI009644, AI 09644)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › 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
- AcrAB efflux pump, multidrug efflux, Salmonella typhimurium, beta-lactam antibiotics, antibiotic resistance, lipophilic side chains, membrane partitioning, outer membrane permeability, nafcillin
- MeSH terms
- Anti-Bacterial Agents, Bacterial Proteins, Cephalosporins, DNA-Binding Proteins, Drug Resistance, Microbial, Microbial Sensitivity Tests, Mutation, Nafcillin, Phenotype, Salmonella typhimurium, Transduction, Genetic
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