ArticleThe Journal of antimicrobial chemotherapy2009
Development of homogeneous expression of resistance in methicillin-resistant Staphylococcus aureus clinical strains is functionally associated with a beta-lactam-mediated SOS response.
Article in The Journal of antimicrobial chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Modulators of gene amplification alter evolution of antibiotic resistance in Staphylococcus aureus.PLoS genetics · 2025Article
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- Genetic and Phenotypic Changes Related to the Development ofAntibiotics (Basel, Switzerland) · 2024Article
- Antimicrobial Peptides and Small Molecules Targeting the Cell Membrane of Staphylococcus aureus.Microbiology and molecular biology reviews : MMBR · 2023Review
- An Interplay of Multiple Positive and Negative Factors Governs Methicillin Resistance in Staphylococcus aureus.Microbiology and molecular biology reviews : MMBR · 2022Review
- Phenotypic and Molecular Characterization of Carbapenem-HeteroresistantAntibiotics (Basel, Switzerland) · 2022Article
- Regulation of Heterogenous LexA Expression inInternational journal of molecular sciences · 2022Article
- Article
- RexAB Promotes the Survival of Staphylococcus aureus Exposed to Multiple Classes of Antibiotics.Antimicrobial agents and chemotherapy · 2021Article
- Effect of β-lactam antibiotic resistance gene expression on the radio-resistance profile ofHeliyon · 2018Article
- Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin-resistant Staphylococcus aureus.Scientific reports · 2018Article
- Antibiotics trigger initiation of SCCmec transfer by inducing SOS responses.Nucleic acids research · 2017Article
- Role of the Stringent Stress Response in the Antibiotic Resistance Phenotype of Methicillin-Resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2016Article
- Antimicrobial heteroresistance: an emerging field in need of clarity.Clinical microbiology reviews · 2015Review
- Ceftaroline is active against heteroresistant methicillin-resistant Staphylococcus aureus clinical strains despite associated mutational mechanisms and intermediate levels of resistance.Antimicrobial agents and chemotherapy · 2014Article
- TCA cycle-mediated generation of ROS is a key mediator for HeR-MRSA survival under β-lactam antibiotic exposure.PloS one · 2014Article
- Targeting of PBP1 by β-lactams determines recA/SOS response activation in heterogeneous MRSA clinical strains.PloS one · 2013Article
- Exposure of clinical MRSA heterogeneous strains to β-lactams redirects metabolism to optimize energy production through the TCA cycle.PloS one · 2013Article
- β-Lactams increase the antibacterial activity of daptomycin against clinical methicillin-resistant Staphylococcus aureus strains and prevent selection of daptomycin-resistant derivatives.Antimicrobial agents and chemotherapy · 2012Article
- VraSR two-component regulatory system contributes to mprF-mediated decreased susceptibility to daptomycin in in vivo-selected clinical strains of methicillin-resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
objectivesOne of the main characteristics of methicillin-resistant Staphylococcus aureus (MRSA) from both hospitals and community is their heterogeneous expression of resistance. Recently, we reported new heterogeneous MRSA isolates phenotypically susceptible to oxacillin despite being mecA positive. These low-level mecA-mediated resistance MRSA strains are very heterogeneous in expression (HeR) and are likely to be clinically relevant since exposure of such isolates to beta-lactams can result in high-level homotypic resistance (HoR). We hypothesized that HeR to HoR selection in these clinically relevant strains may be determined by the pre-existence of a hypermutable population that favours its selection in the presence of oxacillin.
methodsUsing established procedures, SA13011 HeR to HoR selection was performed by using subinhibitory concentrations of oxacillin and examined for mutability. Real-time RT-PCR and transcriptional profiling by DNA microarray were used to compare gene expression between both populations and related genetically modified SA13011 strain.
resultsWe found that HeR/HoR selection by oxacillin was associated with increased mutation rate and oxacillin-mediated SOS response. We determined increased expression of both mecA and SOS response lexA/recA regulators. Mutational inactivation of lexA repressor resulted in a significant decrease in both mutation rate and oxacillin resistance in the HoR cells. Complementation of the lexA mutant strain restored oxacillin resistance to the high levels observed in the corresponding HoR wild-type strain.
conclusionsThe present results support the notion that SOS response is mechanistically involved in generating mutations that, in addition to mecA induction, allow the selection of a highly oxacillin-resistant population.
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