Transfer of penicillin resistance from Streptococcus oralis to Streptococcus pneumoniae identifies murE as resistance determinant
Transfer of penicillin resistance from Streptococcus oralis to Streptococcus pneumoniae identifies murE as resistance determinant
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DOI：
10.1111/mmi.13070
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发表时间：
2015-09
影响因子：
3.6
通讯作者：
K. Todorova;P. Maurer;M. Rieger;T. Becker;N. K. Bui;J. Gray;W. Vollmer;R. Hakenbeck
中科院分区：
文献类型：
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作者：
K. Todorova;P. Maurer;M. Rieger;T. Becker;N. K. Bui;J. Gray;W. Vollmer;R. Hakenbeck
肺炎链球菌的β-内酰胺耐药临床分离株含有改变的青霉素结合蛋白（PBP）基因，偶尔还含有改变的murM，推测是种间基因转移的产物。MurM和MurN负责合成支链脂质II，其为PBP催化的转肽反应的底物。这里我们使用了高水平的β-内酰胺耐药S oralis Uo 5为供体，对敏感的实验菌株S. pneumoniae R6作为受体。令人惊讶的是，哌拉西林抗性转化体不包含PBP基因的改变，但携带编码UDP-N-乙酰胞壁酰三肽合成酶的murEUo 5。murEUo 5的密码子83-183足以赋予抗性表型。此外，与S. pneumoniae R6也可赋予增加的抗性。多个独立的转化产生S. pneumoniae R6衍生物含有murEUo 5、pbp 2xUo 5、pbp 1aUo 5和pbp 2bUo 5，但不含murMUo 5序列;但不能达到供体菌株的耐药水平。S. oralis Uo 5具有一个不寻常的murM，murN缺失。因此，S. oralis Uo 5含有仅具有一个L-Ala残基的肽间桥。这些数据表明，S. oralis Uo 5基于不同PBP和参与肽聚糖生物合成的其它酶的复杂相互作用。
Beta‐lactam resistant clinical isolates of Streptococcus pneumoniae contain altered penicillin‐binding protein (PBP) genes and occasionally an altered murM, presumably products of interspecies gene transfer. MurM and MurN are responsible for the synthesis of branched lipid II, substrate for the PBP catalyzed transpeptidation reaction. Here we used the high‐level beta‐lactam resistant S. oralis Uo5 as donor in transformation experiments with the sensitive laboratory strain S. pneumoniae R6 as recipient. Surprisingly, piperacillin‐resistant transformants contained no alterations in PBP genes but carried murEUo5 encoding the UDP‐N‐acetylmuramyl tripeptide synthetase. Codons 83–183 of murEUo5 were sufficient to confer the resistance phenotype. Moreover, the promoter of murEUo5, which drives a twofold higher expression compared to that of S. pneumoniae R6, could also confer increased resistance. Multiple independent transformations produced S. pneumoniae R6 derivatives containing murEUo5, pbp2xUo5, pbp1aUo5 and pbp2bUo5, but not murMUo5 sequences; however, the resistance level of the donor strain could not be reached. S. oralis Uo5 harbors an unusual murM, and murN is absent. Accordingly, the peptidoglycan of S. oralis Uo5 contained interpeptide bridges with one L‐Ala residue only. The data suggest that resistance in S. oralis Uo5 is based on a complex interplay of distinct PBPs and other enzymes involved in peptidoglycan biosynthesis.