Selvi C Ersoy, Sabrina L Madrigal, Richard A Proctor, Henry F Chambers, Yan Q Xiong, Arnold S Bayer
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引用次数: 0
Abstract
Background: Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to nearly all β-lactam antibiotics under standard testing conditions. However, a novel phenotype exists wherein certain MRSA strains exhibit β-lactam susceptibility in the presence of bicarbonate (termed 'NaHCO3-responsive'), an abundant ion in mammalian tissues and blood. This suggests that specific MRSA infections may be treatable by β-lactams. NaHCO3 responsiveness appears due to effects of NaHCO3 on the expression mecA/PBP2a and other accessory genes required for PBP functionality. mecA expression can be co-regulated by the bla operon regulatory genes, blaI and blaR1.
Objectives: To elucidate the influence of NaHCO3 specifically on the bla operon via investigations of the impact of NaHCO3 on β-lactamase hyper-producing, mecA-negative, borderline oxacillin-resistant Staphylococcus aureus (BORSA) strains.
Methods: Evaluate the effect of NaHCO3 on β-lactam susceptibility via minimum inhibitory concentrations (MIC) assay, expression of genes within the bla operon (blaZ, blaI, blaR1) via RT-qPCR, and β-lactamase (BlaZ) activity via nitrocefinase assay in BORSA.
Results: NaHCO3 enhanced susceptibility to β-lactamase-susceptible β-lactams penicillin and ampicillin. NaHCO3 had no impact on susceptibility to the anti-staphylococcal β-lactams oxacillin and cefazolin, or the anti-MRSA antibiotics vancomycin and daptomycin. NaHCO3 repressed expression of all genes within the bla operon and reduced β-lactamase production.
Conclusions: These data demonstrate that NaHCO3 influences expression of genes within the bla operon, translating to reduced β-lactamase production and enhanced β-lactam susceptibility in BORSA strains. Furthermore, this indicates that the classical blaZ regulators, blaI and blaR1, are the likely mediators of NaHCO3-mediated repression of mecA. However, questions still remain regarding the mechanism via which NaHCO3 regulates the bla operon.
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The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.
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