Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes.
Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes.
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DOI：
10.1099/mic.0.000206
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发表时间：
2016
期刊：
影响因子：
1.5
通讯作者：
Yan Zhang;I. Tatsuno;Ryo Okada;Nanako Hata;M. Matsumoto;M. Isaka;K. Isobe;T. Hasegawa
中科院分区：
文献类型：
--
作者：
Yan Zhang;I. Tatsuno;Ryo Okada;Nanako Hata;M. Matsumoto;M. Isaka;K. Isobe;T. Hasegawa
在日本，据报道链球菌中毒性休克综合征患者的数量正在增加。认为mef（A）基因阳性的大环内酯类耐药emm 1菌株可能导致STSS频率的升高。尽管大环内酯类耐药机制（包括mef（A）耐药）的分析主要在肺炎链球菌中进行，但该基因在化脓链球菌中的作用尚未完全研究。因此，据我们所知，我们建立了第一个mef（A）基因敲除菌株使用emm 1型S。并对红霉素、克拉霉素和阿奇霉素进行了药敏试验。我们发现，抗菌药物的敏感性几乎是相同的亲本菌株。因此，我们建立了另一个基因msr（D）的敲除菌株，该基因位于mef（A）的紧下游。所得菌株的大环内酯抗性显著降低，并且当mef（A）和msr（D）两者被敲除时进一步改变。将msr（D）基因导入大环内酯敏感菌株比导入mef（A）基因赋予更大的抗性。使用另外两种emm 4-和emm 75-型S进一步剖析敲除菌株的红霉素敏感性。化脓菌菌株。我们发现两种菌株的结果几乎相同，除了mef（A）敲除emm 4型，其易感性发生了改变，尽管这种变化小于msr（D）敲除。这些结果表明，mef（A）和msr（D）都参与了S.并且msr（D）基因比mef（A）基因在大环内酯类药物抗性中起更主要的作用。
In Japan, the number of patients with streptococcal toxic shock syndrome is reported to be increasing. mef(A) gene-positive macrolide-resistant emm1 strains are thought to possibly contribute to the rise in the frequency of STSS. Although analyses of macrolide-resistant mechanisms, including mef(A) resistance, have been performed mainly in Streptococcus pneumoniae, the role of this gene in Streptococcus pyogenes has not been completely investigated. Therefore, to the best of our knowledge, we established the first mef(A)-knockout strain using an emm1-type S. pyogenes strain, and tested its susceptibility to erythromycin, clarithromycin and azithromycin. We found that the antimicrobial susceptibilities were almost identical to those of the parental strain. Hence, we established a knockout strain for another gene, msr(D), that is located immediately downstream of mef(A). The macrolide resistances of the resulting strain significantly decreased, and were further altered when both mef(A) and msr(D) were knocked out. The introduction of the msr(D) gene into a macrolide-sensitive strain conferred more resistance than the introduction of the mef(A) gene. The erythromycin susceptibilities of knockout strains were further dissected using two additional emm4- and emm75-type S. pyogenes strains. We found almost identical results for both strains except for the mef(A) knockout emm4 type, whose susceptibility was altered, although the change was less than that for the msr(D) knockout. These results suggest that both mef(A) and msr(D) are involved in macrolide resistance in S. pyogenes, and that the msr(D) gene plays a more predominant role in macrolide resistance than mef(A).