Service de Microbiologie AP-HP, Hôpital Européen Georges Pompidou, Paris, France.
Antimicrob Agents Chemother. 2012 Oct;56(10):5040-5. doi: 10.1128/AAC.00939-12. Epub 2012 Jul 16.
Seventy-four unrelated clinical isolates of Streptococcus pneumoniae harboring the tet(M) gene were studied. Seven strains with low tetracycline (Tc) MICs (0.25 to 0.5 μg/ml) were found to harbor truncated tet(M) alleles that were inactivated by different frameshift mutations. In contrast, five strains bore deletions in the tet(M) promoter region, among which four displayed increased Tc MICs (16 to 64 μg/ml). The same promoter mutations were detected in Tc-resistant mutants selected in vitro from various susceptible strains. Sequence analysis revealed that these deletions might impede the formation of the transcriptional attenuator located immediately upstream of tet(M). Expression in Enterococcus faecalis of a tet(M) reporter gene transcribed from these promoter mutants conferred a level of Tc resistance similar to that observed in the parental S. pneumoniae strains. These results show that different levels of Tc susceptibility found in clinical isolates of S. pneumoniae can be explained by frameshift mutations within tet(M) and by alterations of the upstream transcriptional attenuator.
对 74 株携带 tet(M)基因的无关联肺炎链球菌临床分离株进行了研究。发现 7 株四环素 MIC 值较低（0.25 至 0.5μg/ml）的菌株携带截短的 tet(M)等位基因，这些等位基因因不同的移码突变而失活。相比之下，5 株菌株带有 tet(M)启动子区域的缺失，其中 4 株显示出四环素 MIC 值升高（16 至 64μg/ml）。在体外从各种敏感株中选择的四环素耐药突变株中也检测到了相同的启动子突变。序列分析表明，这些缺失可能会阻碍位于 tet(M)上游的转录衰减子的形成。在粪肠球菌中表达由这些启动子突变转录的 tet(M)报告基因，赋予了与亲本肺炎链球菌株中观察到的相似水平的四环素耐药性。这些结果表明，肺炎链球菌临床分离株中不同水平的四环素敏感性可以通过 tet(M)内的移码突变和上游转录衰减子的改变来解释。
