Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin-susceptible/mecA-positive MRSA strains from Africa
Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin-susceptible/mecA-positive MRSA strains from Africa
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DOI：
10.1093/jac/dkw209
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发表时间：
2016-10-01
影响因子：
5.2
通讯作者：
Tomasz, Alexander
中科院分区：
文献类型：
--
作者：
Chung, Marilyn;Kim, Choon Keun;Tomasz, Alexander
目的：最近对两个非洲国家（安哥拉、圣多美和普林西比）的 MRSA 定植患者和医护人员进行的监测报告称，苯唑西林敏感 MRSA (OS-MRSA) 频繁复苏：这种金黄色葡萄球菌菌株在 mecA DNA 探针中给出阳性结果，但具有易感金黄色葡萄球菌特有的苯唑西林 MIC 值低的特征。耐药表型与 mecA（耐药性的主要遗传决定因素）的这种明显分离促使我们对九种非洲 OS-MRSA 菌株进行更详细的分析。 方法：通过 Etest 和群体分析图谱确定苯唑西林 MIC 值，并在莫匹罗星诱导和不诱导严格应激反应的情况下进行。使用 SDS-PAGE 和蛋白质印迹进行生化分析，用于检测产生的 PBP2A 蛋白。 结果：非洲 MRSA 菌株（ST88-IVa 和 ST8-V）的培养物表现出异质性苯唑西林耐药性，其中大多数细胞表现出低苯唑西林 MIC（千分之一货币符号 0.75 mg/L），但也存在高度耐药的亚群，苯唑西林 MIC 值高达数百mg/L，频率为 10(-4) 至 10(-6)。相同菌株在莫匹罗星诱导严格应激反应后将异质表型“转化”为更均质和更高水平的抗性。经苯唑西林和莫匹罗星诱导后，9个非洲OS-MRSA菌株均产生PBP2A——mecA的蛋白质产物。结论：OS-MRSA的耐药表型与历史上早期MRSA克隆的表型相似。造成 OS-MRSA 异质表型的遗传决定因素的性质仍有待确定。
Objectives: Recent surveillance of MRSA colonizing patients and healthcare workers in two African countries (Angola and Sao Tom, and Principe) reported the frequent recovery of oxacillin-susceptible MRSA (OS-MRSA): Staphylococcus aureus strains that gave positive results with the mecA DNA probe, but had low oxacillin MIC values characteristic of susceptible S. aureus. This apparent dissociation of the drug-resistant phenotype from mecA-the primary genetic determinant of resistance-prompted us to perform a more detailed analysis on nine of the African OS-MRSA strains.Methods:Oxacillin MIC values were determined by Etest and population analysis profiles with and without induction of the stringent stress response by mupirocin. Biochemical profiling using SDS-PAGE followed by western blotting was used for the detection of PBP2A protein produced.Results:Cultures of the African MRSA strains (ST88-IVa and ST8-V) showed heterogeneous oxacillin resistance in which the majority of cells exhibited low oxacillin MICs (a parts per thousand currency sign0.75 mg/L), but highly resistant subpopulations were also present with oxacillin MIC values up to several hundred mg/L and with frequencies of 10(-4) to 10(-6). The same strains after induction of the stringent stress response by mupirocin 'converted' the heterogeneous phenotypes into a more homogeneous and higher level resistance. After induction by oxacillin and mupirocin, each of the nine African OS-MRSA strains produced PBP2A-the protein product of mecA.Conclusions:The resistant phenotype of OS-MRSA resembles the phenotypes of historically early MRSA clones. The nature of genetic determinants responsible for the heterogeneous phenotypes of OS-MRSA remains to be determined.