Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
Sci Rep. 2017 Jul 21;7(1):6154. doi: 10.1038/s41598-017-06329-2.
β-lactam antibiotics target penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is circumvented in methicillin resistant Staphylococcus aureus (MRSA) strains through the expression of an additional PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the Staphylococcal Chromosome Cassette mec (SCCmec) mobile genetic element, of which there are 12 types described to date. Previous investigations aimed at analysing the synergistic activity of two β-lactams, oxacillin and cefoxitin, found that SCCmec type IV community-acquired MRSA strains exhibited increased susceptibility to oxacillin in the presence of cefoxitin, while hospital-acquired MRSA strains were unaffected. However, it is not clear if these differences in β-lactam resistance are indeed a consequence of the presence of the different SCCmec types. To address this question, we have exchanged the SCCmec type I in COL (HA-MRSA) for the SCCmec type IV from MW2 (CA-MRSA). This exchange did not decrease the resistance of COL against oxacillin and cefoxitin, as observed in MW2, indicating that genetic features residing outside of the SCCmec element are likely to be responsible for the discrepancy in oxacillin and cefoxitin synergy against these MRSA strains.
β-内酰胺类抗生素以青霉素结合蛋白（PBPs）为作用靶点，通过抑制其活性来阻止肽聚糖的合成。耐甲氧西林金黄色葡萄球菌（MRSA）通过表达一种额外的 PBP2A 来规避这种抑制作用，这种酶由 mecA 基因编码，该基因位于葡萄球菌染色体盒 mec（SCCmec）可移动遗传元件中，目前已描述了 12 种类型。先前的研究旨在分析两种β-内酰胺类药物，即苯唑西林和头孢西丁的协同作用，结果发现 SCCmec 类型 IV 社区获得性 MRSA 菌株在头孢西丁存在的情况下对苯唑西林的敏感性增加，而医院获得性 MRSA 菌株则不受影响。然而，目前尚不清楚β-内酰胺类耐药性的这些差异是否确实是由于不同 SCCmec 类型的存在所导致的。为了解决这个问题，我们已经将 COL（HA-MRSA）中的 SCCmec 类型 I 替换为 MW2（CA-MRSA）中的 SCCmec 类型 IV。正如在 MW2 中观察到的那样，这种替换并没有降低 COL 对苯唑西林和头孢西丁的耐药性，这表明 SCCmec 元件之外的遗传特征可能是导致这些 MRSA 菌株对苯唑西林和头孢西丁协同作用差异的原因。
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