Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas, USA
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.
J Bacteriol. 2020 Nov 4;202(23). doi: 10.1128/JB.00504-20.
(group B streptococcus [GBS]) is a major cause of infections in newborns, pregnant women, and immunocompromised patients. GBS strain CNCTC10/84 is a clinical isolate that has high virulence in animal models of infection and has been used extensively to study GBS pathogenesis. Two unusual features of this strain are hyperhemolytic activity and hypo-CAMP factor activity. These two phenotypes are typical of GBS strains that are functionally deficient in the CovR-CovS two-component regulatory system. A previous whole-genome sequencing study found that strain CNCTC10/84 has intact and regulatory genes. We investigated CovR-CovS regulation in CNCTC10/84 and discovered that a single-nucleotide insertion in a homopolymeric tract in the promoter region underlies the strong hemolytic activity and weak CAMP activity of this strain. Using isogenic mutant strains, we demonstrate that this single-nucleotide insertion confers significantly decreased expression of and and altered expression of CovR-CovS-regulated genes, including that of genes encoding β-hemolysin and CAMP factor. This single-nucleotide insertion also confers significantly increased GBS survival in human whole blood Group B streptococcus (GBS) is the leading cause of neonatal sepsis, pneumonia, and meningitis. GBS strain CNCTC10/84 is a highly virulent blood isolate that has been used extensively to study GBS pathogenesis for over 20 years. Strain CNCTC10/84 has an unusually strong hemolytic activity, but the genetic basis is unknown. In this study, we discovered that a single-nucleotide insertion in an intergenic homopolymeric tract is responsible for the elevated hemolytic activity of CNCTC10/84.
（GBS）是导致新生儿、孕妇和免疫功能低下患者感染的主要原因。GBS 菌株 CNCTC10/84 是一种临床分离株，在感染动物模型中具有高毒力，已广泛用于研究 GBS 发病机制。该菌株有两个不寻常的特征：高度溶血活性和低 CAMP 因子活性。这两种表型是功能上缺乏 CovR-CovS 双组分调节系统的 GBS 菌株的典型特征。先前的全基因组测序研究发现，菌株 CNCTC10/84 具有完整的 和 调节基因。我们研究了 CNCTC10/84 中的 CovR-CovS 调节，发现 启动子区域中一个同聚核苷酸链中的单个核苷酸插入是该菌株强烈溶血活性和弱 CAMP 活性的基础。使用同源突变菌株，我们证明该单个核苷酸插入导致 和 表达显著降低，以及 CovR-CovS 调节基因的表达改变，包括编码 β-溶血素和 CAMP 因子的基因。该单个核苷酸插入还赋予 GBS 在人全血中显著增加的生存能力。
