A greater effect on clarithromycin resistance of mef associated msr than mef associated msr in Streptococcus pyogenes
A greater effect on clarithromycin resistance of mef associated msr than mef associated msr in Streptococcus pyogenes
复制标题
在化脓性链球菌中，mef 相关 msr 对克拉霉素耐药性的影响大于 mef 相关 msr
DOI：
10.1111/1348-0421.12974
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发表时间：
2022
影响因子：
2.6
通讯作者：
Hasegawa Tadao
中科院分区：
文献类型：
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作者：
Tatsuno Ichiro;Isaka Masanori;Hasegawa Tadao
这些mef(A)‐及其亚类mef(E)‐系统一直被认为是化脓性链球菌对大环内酯类耐药的主要机制之一。然而，我们之前已经证明，位于mef(A)/mef(E)基因下游的themsr(D)基因在这些系统中起主导作用。此外，在先前的研究中，mef(A)‐associatedmsr(D)10‐85的anS. pyogenes菌株（10‐85）比mef(E)‐associatedmsr(D)13‐O‐10的另一菌株（13‐O‐10）表现出更大的克拉霉素最低抑制浓度（MIC）的增加。两个基因编码487个氨基酸残基，其中13个氨基酸残基不同。在这项研究中，我们对themsr(D)基因进行了突变分析，结果表明，导致Asp238被Gly取代的单核苷酸多态性主要与themsr(D)10‐85比themsr(D)13‐O‐10等位基因增加更多的克拉霉素MIC有关。此外，另一个Ser与Arg密码子194的替换部分与themsr(D)10‐85等位基因比themsr(D)13‐O‐10等位基因增加更多有关。
Themef(A)‐ and its subclassmef(E) systems had long been considered to constitute one of the primary macrolide‐resistant mechanisms inStreptococcus pyogenes. However, we have previously demonstrated that themsr(D) gene located immediately downstream of themef(A)/mef(E) genes plays a predominant role in these systems. In previous studies, furthermore,mef(A)‐associatedmsr(D)10‐85of anS. pyogenesstrain (10‐85) exhibited a greater increase in clarithromycin minimum inhibitory concentration (MIC) thanmef(E)‐associatedmsr(D)13‐O‐10of another strain (13‐O‐10). Bothmsr(D) genes encode 487 amino acid residues, 13 amino acid residues of which are different from each other. In this study, we performed mutational analysis of themsr(D) genes and showed that a single‐nucleotide polymorphism to cause a substitution of Asp238 with Gly is mainly associated with the greater increase in clarithromycin MIC by themsr(D)10‐85than by themsr(D)13‐O‐10allele. In addition, another substitution of Ser with Arg at codon 194 is partially associated with the greater increase by themsr(D)10‐85than by themsr(D)13‐O‐10allele.