A PTS EII mutant library in Group A Streptococcus identifies a promiscuous man-family PTS transporter influencing SLS-mediated hemolysis
A PTS EII mutant library in Group A Streptococcus identifies a promiscuous man-family PTS transporter influencing SLS-mediated hemolysis
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DOI：
10.1111/mmi.13573
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发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
McIver, Kevin S.
中科院分区：
文献类型：
--
作者：
Sundar, Ganesh S.;Islam, Emrul;McIver, Kevin S.
A 组链球菌（GAS，化脓性链球菌）是一种革兰氏阳性人类病原体，必须适应独特的宿主环境才能生存。糖代谢和毒力之间的联系已在 GAS 中得到证实，其中磷酸烯醇丙酮酸依赖性磷酸转移酶系统 (PTS) 中的突变体在指数生长过程中表现出链球菌溶血素 S (SLS) 介导的溶血。与亲本 M1T1 MGAS5005 相比，这种早期发生的溶血与小鼠软组织感染模型中病变大小和严重程度的增加相关。为了确定导致这种表型的 PTS 成分，我们插入灭活了 GAS MGAS5005 基因组中 14 个带注释的 PTS EIIC 编码基因，并对这个文库进行代谢和溶血测定，以对每个 EIIC 进行功能表征。研究发现，一些 EII 对 PTS 糖代谢的影响非常有限，而另一些 EII 则相当混杂。由 manLMN 编码的甘露糖特异性 EII 基因座表达为甘露糖诱导操纵子，对 PTS 糖代谢（包括甘露糖）影响最大。重要的是，甘露糖特异性 EII 的成分还可以预防 SLS 介导的溶血的早期发生。有趣的是，这些作用在两种不同的 M1T1 GAS 菌株中并不相同，这凸显了 PTS 适应菌株特定需求的可能多功能性。
The Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human pathogen that must adapt to unique host environments in order to survive. Links between sugar metabolism and virulence have been demonstrated in GAS, where mutants in the phosphoenolpyruvate-dependent phosphotransferase system (PTS) exhibited Streptolysin S (SLS)-mediated hemolysis during exponential growth. This early onset hemolysis correlated with an increased lesion size and severity in a murine soft tissue infection model when compared with parental M1T1 MGAS5005. To identify the PTS components responsible for this phenotype, we insertionally inactivated the 14 annotated PTS EIIC-encoding genes in the GAS MGAS5005 genome and subjected this library to metabolic and hemolysis assays to functionally characterize each EIIC. It was found that a few EIIs had a very limited influence on PTS sugar metabolism, whereas others were fairly promiscuous. The mannose-specific EII locus, encoded by manLMN, was expressed as a mannose-inducible operon that exhibited the most influence on PTS sugar metabolism, including mannose. Importantly, components of the mannose-specific EII also acted to prevent the early onset of SLS-mediated hemolysis. Interestingly, these roles were not identical in two different M1T1 GAS strains, highlighting the possible versatility of the PTS to adapt to strain-specific needs.