Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes.
Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes.
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rocA 上游基因间可变数字串联重复多态性改变化脓性链球菌的毒素产生并增强毒力。
DOI：
10.1128/iai.00258-16
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发表时间：
2016
影响因子：
3.1
通讯作者：
Musser,JamesM
中科院分区：
文献类型：
--
作者：
Zhu,Luchang;Olsen,RandallJ;Horstmann,Nicola;Shelburne,SamuelA;Fan,Jia;Hu,Ye;Musser,JamesM
可变数量串联重复（VNTR）多态性在细菌中普遍存在。然而，只有一小部分进行了功能研究。在这里，我们报告了一种基因间 VNTR 多态性，它改变了化脓性链球菌的毒素产生水平并增加了毒力。多态性的本质是编码传感器激酶的 therocAgene 上游的三串联重复基因座中的一个单位缺失。具有这种多态性的化脓性链球菌菌株会引起人类感染，并产生显着大量的分泌细胞毒素化脓性链球菌NAD酶（SPN）和链球菌溶血素O（SLO）。使用同基因突变株，我们证明，在坏死性筋膜炎小鼠模型中，删除一个或多个串联重复单元可以消除 RocA 的产生，减少 CovR 磷酸化，抑制多种 CovR 调节的毒力因子（例如 SPN 和 SLO），并增加毒力。 VNTR多态性的表型效应与灭活therocAgene的表型效应几乎相同。总之，我们鉴定并鉴定了化脓性链球菌中影响毒素产生和毒力的基因间 VNTR 多态性。这些新发现增强了对 rocAbiology 和 VNTR 多态性在化脓性链球菌中功能的理解。
Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes. The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of therocAgene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating therocAgene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding ofrocAbiology and the function of VNTR polymorphisms in S. pyogenes.