Phosphotransferase System Uptake and Metabolism of the β-Glucoside Salicin Impact Group A Streptococcal Bloodstream Survival and Soft Tissue Infection
Phosphotransferase System Uptake and Metabolism of the β-Glucoside Salicin Impact Group A Streptococcal Bloodstream Survival and Soft Tissue Infection
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DOI：
10.1128/iai.00346-20
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发表时间：
2020-10-01
影响因子：
3.1
通讯作者：
McIver, Kevin S.
中科院分区：
文献类型：
--
作者：
Braza, Rezia Era;Silver, Aliyah B.;McIver, Kevin S.
化脓性链球菌（A组链球菌[GAS]）是一种主要的人类特异性病原体，其成功感染宿主依赖于有效的营养获取。磷酸转移酶系统（PTS）在代谢之前将碳水化合物的输入与其磷酸化偶联，并且与GAS发病机制有关。在MGAS 5005中所有14个注释的PTS通透酶（EIIC）基因的插入突变体文库的筛选中，发现注释的β-葡糖苷PTS转运蛋白（bglP）对人血液中的GAS生长和存活至关重要，并且在另一种M1 T1 GAS菌株5448中得到验证。在5448中，bglP被证明存在于操纵子中，下游是推定的磷酸-β-葡糖苷酶（bglB），上游是预测的抗终止子（licT）。使用5448中β-葡萄糖苷通透酶（bglP）和β-葡萄糖苷酶（bglB）的定义的非极性突变体，我们表明bglB，而不是bglP，对血液中的生长很重要。此外，发现licT-blgPB操纵子的转录被葡萄糖抑制，并被作为唯一碳源的β-葡糖苷水杨苷诱导。对单个bglP和bglB突变体的研究确定了它们影响β-葡糖苷水杨苷的体外生长;然而，只有bglP是其他非β-葡糖苷PTS糖（如果糖和甘露糖）生长所必需的。此外，BglP和BglB的丢失表明它们对于控制小鼠皮下感染期间生物膜形成、链球菌溶血素S（SLS）介导的溶血和局部溃疡性病变进展的毒力相关基因的调节是重要的。因此，我们的研究结果表明，β-葡萄糖苷PTS运输水杨苷和它的代谢可以差异影响软组织感染期间的GAS病理生理学。
Streptococcus pyogenes (group A Streptococcus [GAS)), a major human-specific pathogen, relies on efficient nutrient acquisition for successful infection within its host. The phosphotransferase system (PTS) couples the import of carbohydrates with their phosphorylation prior to metabolism and has been linked to GAS pathogenesis. In a screen of an insertional mutant library of all 14 annotated PTS permease (EIIC) genes in MGAS5005, the annotated beta-glucoside PTS transporter (bglP) was found to be crucial for GAS growth and survival in human blood and was validated in another M1T1 GAS strain, 5448. In 5448, bglP was shown to be in an operon with a putative phospho-beta-glucosidase (bglB) downstream and a predicted antiterminator (licT) upstream. Using defined nonpolar mutants of the beta-glucoside permease (bglP) and beta-glucosidase enzyme (bglB) in 5448, we showed that bglB, not bglP, was important for growth in blood. Furthermore, transcription of the licT-blgPB operon was found to be repressed by glucose and induced by the beta-glucoside salicin as the sole carbon source. Investigation of the individual bglP and bglB mutants determined that they influence in vitro growth in the beta-glucoside salicin; however, only bglP was necessary for growth in other non-beta-glucoside PTS sugars, such as fructose and mannose. Additionally, loss of BglP and BglB suggests that they are important for the regulation of virulence-related genes that control biofilm formation, streptolysin S (SLS)-mediated hemolysis, and localized ulcerative lesion progression during subcutaneous infections in mice. Thus, our results indicate that the beta-glucoside PTS transports salicin and its metabolism can differentially influence GAS pathophysiology during soft tissue infection.