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Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes

机译:rocA上游的基因间可变数串联重复多态性改变产毒链球菌并提高了化脓性链球菌的毒力。

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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 the rocA gene 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 the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes.
机译:细菌中普遍存在可变数目的串联重复(VNTR)多态性。但是,仅对其中的一小部分进行了功能研究。在这里,我们报告了一种基因间的VNTR多态性,可赋予毒素生产水平变化和化脓性链球菌增加的毒力。多态性的性质是在编码传感器激酶的 rocA 基因上游的三串重复基因座中的一个单元缺失。具有这种多态性的化脓性链球菌菌株引起人感染,并产生大量的分泌的细胞毒素,即化脓性链球菌NADase(SPN)和链球菌溶血素O(SLO)。使用等基因突变株,我们证明删除一个或多个串联重复可废除RocA产生,减少CovR磷酸化,降低抑制多个CovR调节的毒力因子(例如SPN和SLO)以及在坏死性筋膜炎小鼠模型中的毒力。 VNTR多态性的表型作用与灭活 rocA 基因的作用几乎相同。总之,我们在化脓性链球菌中鉴定并表征了一种基因间VNTR多态性,该多态性影响毒素的产生和毒力。这些新发现增强了对 rocA 生物学和化脓性链球菌VNTR多态性功能的了解。

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