Identification of Point Mutations in Clinical Staphylococcus aureus Strains That Produce Small-Colony Variants Auxotrophic for Menadione
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Staphylococcus aureus small-colony variants (SCVs) are implicated in chronic and relapsing infections that are difficult to diagnose and treat. Despite many years of study, the underlying molecular mechanisms and virulence effect of the small-colony phenotype remain incompletely understood. We sequenced the genomes of five S. aureus SCV strains recovered from human patients and discovered previously unidentified nonsynonymous point mutations in three genes encoding proteins in the menadione biosynthesis pathway. Analysis of genetic revertants and complementation with wild-type alleles confirmed that these mutations caused the SCV phenotype and decreased virulence for mice.
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These mutations were similar to those reported previously in clinical isolates.
“These mutations were similar to those reported previously in clinical isolates and confirm that the SCV phenotype was due to genetic changes rather than to epigenetic effects or the physiological response of the bacterium to oxidative stress (15, 17).”
From Staphylococcus aureus Adapts to Oxidative Stress by Producing H <sub>2</sub> O <sub>2</sub> -Resistant Small-Colony Variants via the SOS Response (2015) · cites this paper as [15]
SCVs can restore the population of wild-type bacteria via the repair of mutations or acquisition of suppressor mutations that restore the function of mutated gene products.
“A key part of such an ensurance policy is the ability to restore the population of wild-type bacteria, which SCVs can do via the repair of mutations or acquisition of suppressor mutations that restore the function of mutated gene products (15, 17).”
From Staphylococcus aureus Adapts to Oxidative Stress by Producing H <sub>2</sub> O <sub>2</sub> -Resistant Small-Colony Variants via the SOS Response (2015) · cites this paper as [15]
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- Authors
- Dean, M. A., Olsen, R. J., Long, S. W., Rosato, A. E., & Musser, J. M.
- Affiliations
- Houston Methodist (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2014-04
- Volume
- 82
- Issue
- 4
- Pages
- 1600-1605
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC3993378
- OpenAlex
- W2097252391
- Cited by
- 69
- References
- 38
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 2 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 2
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Houston Methodist Hospital
- National Institutes of Health
- Houston Methodist Research Institute
- National Institute of Allergy and Infectious Diseases (R01AI080688)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Staphylococcus aureus, small colony variants, virulence, revertants, complementation, chronic infection, infection relapse
- MeSH terms
- Animals, Anti-Bacterial Agents, Disease Models, Animal, Gentamicins, Microbial Sensitivity Tests, Phenotype, Staphylococcal Infections, Staphylococcus aureus, Virulence, Genome, Bacterial, Point Mutation, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Vitamin K 3, Mice
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