摘要

由于mecA基因的存在，大多数耐甲氧西林金黄色葡萄球菌（MRSA）菌株对β-内酰胺抗生素具有抗性，编码对几乎所有β-内酰胺抗生素具有低亲和力的额外青霉素结合蛋白（PBP2A）。最近，在从人类和奶牛中回收的金黄色葡萄球菌分离株中鉴定出新的抗性决定簇-mecC基因。尽管对β-内酰胺抗生素的MIC一般较低，但具有mecC决定簇的MRSA菌株在最佳遗传背景下也能够表达高水平的苯唑西林抗性。为了测试广泛的β-内酰胺选择对具有高水平抗生素抗性的mecC携带菌株的出现的影响，我们将携带mecC的MRSA菌株LGA251原型暴露于增加浓度的苯唑西林。 LGA251能够快速适应生长培养基中高浓度的苯唑西林。在这种具有增加的苯唑西林抗性水平的实验室突变体中，我们鉴定了与mecC调控系统无关的基因突变，表明遗传背景在建立苯唑西林抗性水平中起重要作用。我们的数据还表明，严格的应激反应在携带mecC决定簇的MRSA菌株的β-内酰胺抗生素抗性表型中起关键作用。

Most methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to beta-lactam antibiotics due to the presence of the mecA gene, encoding an extra penicillin-binding protein (PBP2A) that has low affinity for virtually all beta-lactam antibiotics. Recently, a new resistance determinant—the mecC gene—was identified in S. aureus isolates recovered from humans and dairy cattle. Although having typically low MICs to beta-lactam antibiotics, MRSA strains with the mecCdeterminant are also capable of expressing high levels of oxacillin resistance when in an optimal genetic background. In order to test the impact of extensive beta-lactam selection on the emergence of mecC-carrying strains with high levels of antibiotic resistance, we exposed the prototype mecC-carrying MRSA strain, LGA251, to increasing concentrations of oxacillin. LGA251 was able to rapidly adapt to high concentrations of oxacillin in growth medium. In such laboratory mutants with increased levels of oxacillin resistance, we identified mutations in genes with no relationship to the mecC regulatory system, indicating that the genetic background plays an important role in the establishment of the levels of oxacillin resistance. Our data also indicate that the stringent stress response plays a critical role in the beta-lactam antibiotic resistance phenotype of MRSA strains carrying the mecC determinant.

http://aac.asm.org/content/61/3/e02500-16.short