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Subinhibitory fluoroquinolone exposure selects for reduced beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus and alterations in the SOS-mediated response.
Res Microbiol 2009; 160(3):187-92RM

Abstract

Growth of fluoroquinolone (FQ)-susceptible methicillin-resistant Staphylococcus aureus (MRSA) in the presence of sub-MIC FQ has been shown to enhance methicillin resistance in traditional nosocomial MRSA isolates. We aimed to confirm this phenomenon in nine community-associated MRSA (CA-MRSA) clinical isolates, and to identify candidate genes that might account for this unusual phenotype. Overnight growth of CA-MRSA strains in tryptic soy broth containing a subinhibitory concentration of either ciprofloxacin or levofloxacin resulted in a concentration-related increase in the number of colonies that grew on nafcillin agar, such that about one CFU in four exhibited significantly higher resistance to nafcillin, with only a modest increase in FQ MIC. No mutations were found in the quinolone-resistance determining region of gyrA and grlA. DNA microarray studies of a representative levofloxacin-exposed clone found that gene expression was increased for 53 open reading frames (ORFs), including norR and mecA, and decreased for 10. The majority of these ORFs encode regulatory and stress response proteins. In conclusion, sublethal exposure to FQ alters the SOS response in CA-MRSA and selects in a non-lethal manner for stable mutants with enhanced expression of methicillin resistance.

Authors+Show Affiliations

Division of Infectious Diseases, San Francisco General Hospital, University of California, San Francisco, CA 94110, USA. pierre.tattevin@chu-rennes.frNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19366630

Citation

Tattevin, Pierre, et al. "Subinhibitory Fluoroquinolone Exposure Selects for Reduced Beta-lactam Susceptibility in Methicillin-resistant Staphylococcus Aureus and Alterations in the SOS-mediated Response." Research in Microbiology, vol. 160, no. 3, 2009, pp. 187-92.
Tattevin P, Basuino L, Chambers HF. Subinhibitory fluoroquinolone exposure selects for reduced beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus and alterations in the SOS-mediated response. Res Microbiol. 2009;160(3):187-92.
Tattevin, P., Basuino, L., & Chambers, H. F. (2009). Subinhibitory fluoroquinolone exposure selects for reduced beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus and alterations in the SOS-mediated response. Research in Microbiology, 160(3), pp. 187-92. doi:10.1016/j.resmic.2009.03.003.
Tattevin P, Basuino L, Chambers HF. Subinhibitory Fluoroquinolone Exposure Selects for Reduced Beta-lactam Susceptibility in Methicillin-resistant Staphylococcus Aureus and Alterations in the SOS-mediated Response. Res Microbiol. 2009;160(3):187-92. PubMed PMID: 19366630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subinhibitory fluoroquinolone exposure selects for reduced beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus and alterations in the SOS-mediated response. AU - Tattevin,Pierre, AU - Basuino,Li, AU - Chambers,Henry F, Y1 - 2009/04/12/ PY - 2008/11/06/received PY - 2009/03/10/revised PY - 2009/03/23/accepted PY - 2009/4/16/entrez PY - 2009/4/16/pubmed PY - 2009/8/4/medline SP - 187 EP - 92 JF - Research in microbiology JO - Res. Microbiol. VL - 160 IS - 3 N2 - Growth of fluoroquinolone (FQ)-susceptible methicillin-resistant Staphylococcus aureus (MRSA) in the presence of sub-MIC FQ has been shown to enhance methicillin resistance in traditional nosocomial MRSA isolates. We aimed to confirm this phenomenon in nine community-associated MRSA (CA-MRSA) clinical isolates, and to identify candidate genes that might account for this unusual phenotype. Overnight growth of CA-MRSA strains in tryptic soy broth containing a subinhibitory concentration of either ciprofloxacin or levofloxacin resulted in a concentration-related increase in the number of colonies that grew on nafcillin agar, such that about one CFU in four exhibited significantly higher resistance to nafcillin, with only a modest increase in FQ MIC. No mutations were found in the quinolone-resistance determining region of gyrA and grlA. DNA microarray studies of a representative levofloxacin-exposed clone found that gene expression was increased for 53 open reading frames (ORFs), including norR and mecA, and decreased for 10. The majority of these ORFs encode regulatory and stress response proteins. In conclusion, sublethal exposure to FQ alters the SOS response in CA-MRSA and selects in a non-lethal manner for stable mutants with enhanced expression of methicillin resistance. SN - 1769-7123 UR - https://www.unboundmedicine.com/medline/citation/19366630/Subinhibitory_fluoroquinolone_exposure_selects_for_reduced_beta_lactam_susceptibility_in_methicillin_resistant_Staphylococcus_aureus_and_alterations_in_the_SOS_mediated_response_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0923-2508(09)00025-4 DB - PRIME DP - Unbound Medicine ER -