ArticleAntimicrobial agents and chemotherapy2013
Redefining the role of the β-lactamase locus in methicillin-resistant Staphylococcus aureus: β-lactamase regulators disrupt the MecI-mediated strong repression on mecA and optimize the phenotypic expression of resistance in strains with constitutive mecA expression.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 42 citations in OpenAlex.
- Distinct genetic programs drive antibiotic resistance and intracellular invasion in emerging MRSA strains.mSystems · 2026Article
- Distribution and characteristics of methicillin-resistant staphylococci from non-clinical environments in southern Vietnam.BMC microbiology · 2026Article
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- Description of high-altitude, cold-adaptive, metabolically versatileMicrobiology spectrum · 2025Article
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- Crosstalk involving two-component systems inJournal of bacteriology · 2024Review
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- Natural transformation allows transfer of SCCmec-mediated methicillin resistance in Staphylococcus aureus biofilms.Nature communications · 2022Article
- Early-Onset Neonatal Sepsis in Low- and Middle-Income Countries: Current Challenges and Future Opportunities.Infection and drug resistance · 2022Review
- Whole-genome analysis uncovers loss of blaZ associated with carriage isolates belonging to methicillin-resistant Staphylococcus aureus (MRSA) clone ST5-VI in Cape Verde.Journal of global antimicrobial resistance · 2021Article
- Comparative Transcriptomic Analysis of Staphylococcus aureus Associated with Periprosthetic Joint Infection under in Vivo and in Vitro Conditions.The Journal of molecular diagnostics : JMD · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Epidemiology of β-Lactamase-Producing Pathogens.Clinical microbiology reviews · 2020Review
- Constructing and deconstructing the bacterial cell wall.Protein science : a publication of the Protein Society · 2020Review
- Genome Sequence of a Highly VirulentCurrent genomics · 2020Article
- The Quinazolinone Allosteric Inhibitor of PBP 2a Synergizes with Piperacillin and Tazobactam against Methicillin-Resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2019Article
- Characterization of Staphylococcal Cassette ChromosomemSphere · 2018Article
- Novel methicillin resistance gene mecD in clinical Macrococcus caseolyticus strains from bovine and canine sources.Scientific reports · 2017Article
- Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA.Nature chemical biology · 2015Article
- Transduction of staphylococcal cassette chromosome mec elements between strains of Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to β-lactam chemotherapy, Staphylococcus aureus has acquired two resistance determinants: blaZ, coding for β-lactamase, which confers resistance to penicillins only, and mecA, coding for an extra cell wall cross-linking enzyme with reduced affinity for virtually all other β-lactams. The transcriptional control of both resistance determinants is regulated by homologous repressors (BlaI and MecI, respectively) and sensor inducers (BlaR1 and MecR1, respectively). There is a cross-talk between the two regulatory systems, and it has been demonstrated that bla regulators stabilize the mecA acquisition. In a recent study, we have unexpectedly observed that in most MRSA strains, there was no significant change in the resistance phenotype upon the overexpression in trans of a MecI repressor, whereas in those few strains negative for the bla locus, there was a massive decrease of resistance (D. C. Oliveira and H. de Lencastre, PLoS One 6:e23287, 2011). Here, we demonstrate that, contrary to what is currently accepted, the bla regulatory system efficiently disrupts the strong MecI-mediated repression on mecA, enabling the optimal expression of resistance. This effect appears to be due to the formation of MecI::BlaI heterodimers that might bind less efficiently to the mecA promoter and become nonfunctional due to the proteolytic inactivation of the BlaI monomer. In addition, we have also observed that the presence of bla regulators may enhance dramatically the expression of β-lactam resistance in MRSA strains with constitutive mecA expression, compensating for the fitness cost imposed by the large β-lactamase plasmid. These observations point to important unrecognized roles of the bla locus for the expression of the methicillin-resistant S. aureus (MRSA) phenotype.
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