Stochastic expression of a multiple antibiotic resistance activator confers transient resistance in single cells
Open accessAbstract
Transient resistance can allow microorganisms to temporarily survive lethal concentrations of antibiotics. This can be accomplished through stochastic mechanisms, where individual cells within a population display diverse phenotypes to hedge against the appearance of an antibiotic. To date, research on transient stochastic resistance has focused primarily on mechanisms where a subpopulation of cells enters a dormant, drug-tolerant state. However, a fundamental question is whether stochastic gene expression can also generate variable resistance levels among growing cells in a population. We hypothesized that stochastic expression of antibiotic-inducible resistance mechanisms might play such a role. To investigate this, we focused on a prototypical example of such a system: the multiple antibiotic resistance activator MarA. Previous studies have shown that induction of MarA can lead to a multidrug resistant phenotype at the population level. We asked whether MarA expression also has a stochastic component, even when uninduced. Time lapse microscopy showed that isogenic cells express heterogeneous, dynamic levels of MarA, which were correlated with transient antibiotic survival. This finding has important clinical implications, as stochastic expression of resistance genes may be widespread, allowing populations to hedge against the sudden appearance of an antibiotic.
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In bacterial isogenic variants, although cells contain the same genetic material, their protein levels can vary due to stochastic events associated with gene expression and regulation.
“In bacterial isogenic variants, although the cells contain the same genetic material, their protein levels can vary due to stochastic events associated with gene expression and regulation [31,32].”
From Microbiota of Cheese Ecosystems: A Perspective on Cheesemaking (2025) · cites this paper as [31]
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- Authors
- El Meouche, I., Siu, Y., & Dunlop, M. J.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Dunlop, Mary J.
- Venue
- Scientific Reports
- Published
- 2016-01-13
- Volume
- 6
- Issue
- 1
- Pages
- 19538-19538
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4725842
- OpenAlex
- W2240061877
- Cited by
- 120
- References
- 53
- Citations by year
- 2026: 7 · 2025: 21 · 2024: 8 · 2023: 16 · 2022: 14 · 2021: 11 · 2020: 7 · 2019: 11 · 2018: 10 · 2017: 13 · 2016: 2
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI102922)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- Kahramanmaraş, multiple antibiotic resistance, stochastic gene expression, antibiotic tolerance, multidrug resistance, single-cell heterogeneity
- MeSH terms
- Anti-Bacterial Agents, Carbenicillin, DNA-Binding Proteins, Escherichia coli, Microbial Sensitivity Tests, Gene Expression, Gene Expression Regulation, Bacterial, Drug Resistance, Multiple, Bacterial, Escherichia coli Proteins, Microbial Viability
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