Functional Predominance of msr(D), Which Is More Effective as mef(A)-Associated Than mef(E)-Associated, Over mef(A)/mef(E) in Macrolide Resistance in Streptococcus pyogenes
Functional Predominance of msr(D), Which Is More Effective as mef(A)-Associated Than mef(E)-Associated, Over mef(A)/mef(E) in Macrolide Resistance in Streptococcus pyogenes
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msr(D) 的功能优势，与 mef(A) 相关比 mef(E) 相关更有效，在化脓性链球菌的大环内酯耐药性中优于 mef(A)/mef(E)
DOI：
10.1089/mdr.2017.0277
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发表时间：
2018
影响因子：
2.6
通讯作者：
Hasegawa Tadao
中科院分区：
文献类型：
--
作者：
Tatsuno Ichiro;Isaka Masanori;Masuno Katsuaki;Hata Nanako;Matsumoto Masakado;Hasegawa Tadao
尽管mef（A）及其亚类mef（E）基因长期以来被认为在基于大环内酯类药物外排的耐药中起核心作用，但我们先前已证明，位于mef（A）基因下游的mef（D）基因在化脓性链球菌大环内酯类药物耐药中起主导作用。mef（A）和mef（E）基因由不同的遗传元件携带，并且据报道与mef（A）相关的抗性高于与mef（E）相关的抗性;因此，我们进一步研究了mef（A）/mef（E）及其相关msr（D）的功能相关性。我们建立了另外的mef（A）-、mef（E）-及其相关的msr（D）-敲除菌株，并证实msr（D）优于mef（A）/mef（E）。此外，我们还将mef（A）、mef（E）及其相关的msr（D）基因导入到mef（A）/mef（E）-msr（D）双敲除菌株和mef（A）/mef（E）阴性菌株中进行了实验。Neithermef（A）和normef（E）基因对红霉素耐药性有影响。然而，两种联合msr（D）均表现出显著的效应，并且与ef（A）联合msr（D）的效应大于与ef（E）联合msr（D）的效应。这些结果表明，在至少一些患者中，基于外排的大环内酯类药物耐药性中，msr（D）的总体功能优势超过mef（A）/mef（E）。化脓性菌株此外，mef（A）系统比mef（E）系统具有更高的抗性，这至少部分地归因于与mef（A）和mef（E）相关的msr（D）的功能差异。
Althoughmef(A) and its subclassmef(E) genes have long been considered to play a central role in macrolide efflux-based resistance, we have previously demonstrated that themsr(D) gene located immediately downstream of themef(A) gene plays a predominant role inStreptococcus pyogenesmacrolide resistance. Themef(A) andmef(E) genes are carried by different genetic elements and the resistance associated withmef(A) was reported to be higher than that associated withmef(E); therefore, we further investigated the functional relevance ofmef(A)/mef(E) and its associatedmsr(D). We established additionalmef(A)-,mef(E)-, and their associatedmsr(D)-knockout strains and confirmed the predominance ofmsr(D) overmef(A)/mef(E). In addition, we performed experiments introducingmef(A),mef(E), and their associatedmsr(D) genes intomef(A)/mef(E)-msr(D) double-knockout andmef(A)/mef(E) negative strains. Neithermef(A) normef(E) genes had effects on erythromycin resistance. However, both associatedmsr(D) showed significant effects, and themef(A)-associatedmsr(D) exhibited more effect than themef(E)-associated one. These results suggest that an overall functional predominance ofmsr(D) overmef(A)/mef(E) is conceivable in efflux-based macrolide resistance in at least someS. pyogenesstrains. Furthermore, the higher resistance ofmef(A) system overmef(E) system could be derived at least in part from functional differences ofmef(A)- andmef(E)-associatedmsr(D).