ArticlePloS one2013
The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the stringent stress response.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 102 citations in OpenAlex.
- Prevalence and abundance of selected genes conferring macrolide resistance genes in COPD patients during maintenance treatment with azithromycin.Antimicrobial resistance and infection control · 2020Trial
- An Achilles' heel for methicillin-resistantAntimicrobial agents and chemotherapy · 2026Review
- Genomic Characterization and Virulence Determinants ofAntibiotics (Basel, Switzerland) · 2026Article
- Methicillin-ResistantInternational journal of molecular sciences · 2026Review
- Mutation of lipoprotein processing pathway geneAntimicrobial agents and chemotherapy · 2026Article
- Phosphorylation of Staphylococcus aureus β-lactamase, a prerequisite to its sequestration on the cytoplasmic membrane.Protein science : a publication of the Protein Society · 2025Article
- Skin mycobiota-mediated antagonism against Staphylococcus aureus through a modified fatty acid.Current biology : CB · 2025Article
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- Methicillin-resistantCurrent pharmaceutical biotechnology · 2025Review
- Potential Therapeutic Targets for Combination Antibody Therapy AgainstAntibiotics (Basel, Switzerland) · 2024Review
- Two codependent routes lead to high-level MRSA.Science (New York, N.Y.) · 2024Article
- Combinations ofAntibiotics (Basel, Switzerland) · 2024Article
- Integrating multi-wet laboratory diagnostics to study staphylococci in animals in Uganda.BMC microbiology · 2024Article
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- Proteomic assay for rapid characterisation of Staphylococcus aureus antimicrobial resistance mechanisms directly from blood cultures.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistantAntimicrobial agents and chemotherapy · 2024Article
- mSphere of Influence: Targeting bacterial signaling and metabolism to overcome antimicrobial resistance.mSphere · 2024Article
- High-throughput investigation of genetic design constraints in domesticated Influenza A Virus for transient gene delivery.bioRxiv : the preprint server for biology · 2024Article
- Molecular Determinants of β-Lactam Resistance in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2023Review
- Molecular Surveillance of MRSA in Raw Milk Provides Insight into MRSA Cross Species Evolution.Microbiology spectrum · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedMilheirço, Catarina [corrected to Milheiriço, Catarina]
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
All methicillin resistant S. aureus (MRSA) strains carry an acquired genetic determinant--mecA or mecC--which encode for a low affinity penicillin binding protein -PBP2A or PBP2A'--that can continue the catalysis of peptidoglycan transpeptidation in the presence of high concentrations of beta-lactam antibiotics which would inhibit the native PBPs normally involved with the synthesis of staphylococcal cell wall peptidoglycan. In contrast to this common genetic and biochemical mechanism carried by all MRSA strains, the level of beta-lactam antibiotic resistance shows a very wide strain to strain variation, the mechanism of which has remained poorly understood. The overwhelming majority of MRSA strains produce a unique--heterogeneous--phenotype in which the great majority of the bacteria exhibit very poor resistance often close to the MIC value of susceptible S. aureus strains. However, cultures of such heterogeneously resistant MRSA strains also contain subpopulations of bacteria with extremely high beta-lactam MIC values and the resistance level and frequency of the highly resistant cells in such strain is a characteristic of the particular MRSA clone. In the study described in this communication, we used a variety of experimental models to understand the mechanism of heterogeneous beta-lactam resistance. Methicillin-susceptible S. aureus (MSSA) that received the mecA determinant in the laboratory either on a plasmid or in the form of a chromosomal SCCmec cassette, generated heterogeneously resistant cultures and the highly resistant subpopulations that emerged in these models had increased levels of PBP2A and were composed of bacteria in which the stringent stress response was induced. Each of the major heterogeneously resistant clones of MRSA clinical isolates could be converted to express high level and homogeneous resistance if the growth medium contained an inducer of the stringent stress response.
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