碳酸氢钠调节临界耐苯唑西林金黄色葡萄球菌（BORSA）中的bla操纵子和β-内酰胺敏感性。
NaHCO3 modulates the bla operon and β-lactam susceptibility in borderline oxacillin-resistant Staphylococcus aureus (BORSA).
作者信息
Ersoy Selvi C, Madrigal Sabrina L, Proctor Richard A, Chambers Henry F, Xiong Yan Q, Bayer Arnold S
机构信息
Division of Infection Disease, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
出版信息
J Antimicrob Chemother. 2025 Mar 3;80(3):676-681. doi: 10.1093/jac/dkae455.
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.
背景
耐甲氧西林金黄色葡萄球菌（MRSA）在标准检测条件下对几乎所有β-内酰胺类抗生素耐药。然而，存在一种新的表型，某些MRSA菌株在碳酸氢盐存在下表现出β-内酰胺敏感性（称为“NaHCO₃反应性”），碳酸氢盐是哺乳动物组织和血液中丰富的离子。这表明特定的MRSA感染可能可用β-内酰胺类药物治疗。NaHCO₃反应性似乎是由于NaHCO₃对mecA/PBP2a表达以及PBP功能所需的其他辅助基因的影响。mecA表达可由bla操纵子调节基因blaI和blaR1共同调节。
目的
通过研究NaHCO₃对超产β-内酰胺酶、mecA阴性、对苯唑西林耐药性临界的金黄色葡萄球菌（BORSA）菌株的影响，阐明NaHCO₃对bla操纵子的具体影响。
方法
通过最低抑菌浓度（MIC）测定评估NaHCO₃对β-内酰胺敏感性的影响，通过RT-qPCR评估bla操纵子内基因（blaZ、blaI、blaR1）的表达，并通过硝基头孢菌素酶测定评估BORSA中的β-内酰胺酶（BlaZ）活性。
结果
NaHCO₃增强了对β-内酰胺酶敏感的β-内酰胺类药物青霉素和氨苄西林的敏感性。NaHCO₃对苯唑西林和头孢唑林等抗葡萄球菌β-内酰胺类药物或万古霉素和达托霉素等抗MRSA抗生素的敏感性没有影响。NaHCO₃抑制了bla操纵子内所有基因的表达并减少了β-内酰胺酶的产生。
结论
这些数据表明，NaHCO₃影响bla操纵子内基因的表达，导致BORSA菌株中β-内酰胺酶产生减少和β-内酰胺敏感性增强。此外，这表明经典的blaZ调节因子blaI和blaR1可能是NaHCO₃介导的mecA抑制的介质。然而，关于NaHCO₃调节bla操纵子的机制仍然存在问题。
Zotero 插件