Cited by 273Antimicrobial Resistance in StaphylococcusBacterial Genetics and BiotechnologyEvolution and Genetic Dynamics

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Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin

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Cirz, Ryan T., Jones, Marcus B., Gingles, Neill A., Minogue, Timothy D., Jarrahi, Behnam, Peterson, Scott N., Romesberg, Floyd E.·2007·Journal of Bacteriology

DOI 10.1128/jb.01464-06PMC PMC1797410

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Abstract

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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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.
ORCID: Cirz, Ryan T.
Jones, Marcus B.
Minogue, Timothy D.
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
DOI: 10.1128/jb.01464-06
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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Complete and SOS-Mediated Response of Staphylococcus aureus to the Antibiotic Ciprofloxacin

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