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Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin
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Staphylococcus aureus infections can be difficult to treat due to both multidrug resistance and the organism's remarkable ability to persist in the host. Persistence and the evolution of resistance may be related to several complex regulatory networks, such as the SOS response, which modifies transcription in response to environmental stress. To understand how S. aureus persists during antibiotic therapy and eventually emerges resistant, we characterized its global transcriptional response to ciprofloxacin. We found that ciprofloxacin induces prophage mobilization as well as significant alterations in metabolism, most notably the up-regulation of the tricarboxylic acid cycle. In addition, we found that ciprofloxacin induces the SOS response, which we show, by comparison of a wild-type strain and a non-SOS-inducible lexA mutant strain, includes the derepression of 16 genes. While the SOS response of S. aureus is much more limited than those of Escherichia coli and Bacillus subtilis , it is similar to that of Pseudomonas aeruginosa and includes RecA, LexA, several hypothetical proteins, and a likely error-prone Y family polymerase whose homologs in other bacteria are required for induced mutation. We also examined induced mutation and found that either the inability to derepress the SOS response or the lack of the LexA-regulated polymerase renders S. aureus unable to evolve antibiotic resistance in vitro in response to UV damage. The data suggest that up-regulation of the tricarboxylic acid cycle and induced mutation facilitate S. aureus persistence and evolution of resistance during antibiotic therapy.
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“In contrast, the mutant lacking functional dinB (which is not part of the S. aureus SOS regulon [62]) had only a slight defect in H2O2-induced SCV formation (Fig. 3A).”
From Staphylococcus aureus Adapts to Oxidative Stress by Producing H 2 O 2 -Resistant Small-Colony Variants via the SOS Response (2015) · cites this paper as [62]
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Metadata
- Authors
- Cirz, R. T., Jones, M. B., Gingles, N. A., Minogue, T. D., Jarrahi, B., Peterson, S. N., & Romesberg, F. E.
- Affiliations
- Scripps Research Institute (US)
- Pathogen Functional Genomics Resource Center (PFGRC), The Institute for Genomic Research, Rockville, Maryland 20850
- Corresponding author
- Romesberg, Floyd E.
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2007-01-15
- Volume
- 189
- Issue
- 2
- Pages
- 531-539
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC1797410
- OpenAlex
- W1991848397
- Cited by
- 273
- References
- 46
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 22 · 2023: 15 · 2022: 14 · 2021: 20 · 2020: 19 · 2019: 14 · 2018: 13 · 2017: 8 · 2016: 12 · 2015: 11 · 2014: 10 · 2013: 16 · 2012: 17
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01ai15447-36-0-3)
- Office of Naval Research
- National Institute of Allergy and Infectious Diseases (N01 AI015447)
- 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 › Genetics › Evolution and Genetic Dynamics
- Keywords
- Staphylococcus aureus, ciprofloxacin, SOS response, antibiotic resistance, bacterial persistence, TCA cycle, LexA, RecA, induced mutation, UV damage
- MeSH terms
- Anti-Bacterial Agents, Bacterial Proteins, Ciprofloxacin, Citric Acid Cycle, Mutation, SOS Response, Genetics, Staphylococcus aureus, Ultraviolet Rays, Gene Expression Regulation, Bacterial, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Drug Resistance, Bacterial
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