Department of Medical Laboratory, College of Applied Medical Sciences in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom.
Microbiol Spectr. 2024 Nov 5;12(11):e0197024. doi: 10.1128/spectrum.01970-24. Epub 2024 Oct 14.
(or group B , GBS) is a leading cause of neonatal sepsis and meningitis globally. To sense and respond to variations in its environment, GBS possesses multiple two-component regulatory systems (TCSs), such as LytSR. Here, we aimed to investigate the role of LytSR in GBS pathogenicity. We generated an isogenic knockout mutant in a clinical GBS isolate and used a combination of phenotypic assays and murine models to investigate the contribution of to the colonization and invasive properties of GBS. Deletion of the gene in the GBS chromosome resulted in significantly higher survival rates in mice during sepsis, accompanied by reduced bacterial loads in blood, lung, spleen, kidney, and brain tissues compared to infection with the wild-type strain. In a mouse model of GBS vaginal colonization, we also observed that the knockout mutant was cleared more readily from the vaginal tract compared to its wild-type counterpart. Interestingly, lower levels of proinflammatory cytokines were found in the serum of mice infected with the mutant. Our results demonstrate that the LytSR TCS plays a key role in GBS tissue invasion and pathogenesis, and persistence of mucosal colonization.IMPORTANCEgroup B or GBS) is a common commensal of the female urogenital tract and one of WHO's priority pathogens. The bacterium has evolved mechanisms to adapt and survive in its host, many of which are regulated via two-component signal transduction systems (TCSs); however, the exact contributions of TCSs toward GBS pathogenicity remain largely obscure. We have constructed a TCS deficient mutant in a CC-17 hypervirulent GBS clinical isolate. Using murine models, we showed that LytSR regulatory system is essential for vaginal colonization via promoting biofilm production. We also observed that deficiency led to significantly attenuated virulence properties and lower levels of proinflammatory cytokines in blood. Our findings are of significant importance in that they unveil a previously unreported role for LytSR in GBS and pave the way toward a better understanding of its ability to transition from an innocuous commensal to a deadly pathogen.
（或 B 组链球菌，GBS）是全球新生儿败血症和脑膜炎的主要原因。为了感知和响应其环境的变化，GBS 拥有多种双组分调节系统（TCS），如 LytSR。在这里，我们旨在研究 LytSR 在 GBS 致病性中的作用。我们在临床 GBS 分离株中生成了一个同源缺失突变体，并结合表型测定和小鼠模型来研究缺失对 GBS 定植和侵袭特性的贡献。在 GBS 染色体中缺失基因导致小鼠败血症中的存活率显著提高，与野生型菌株感染相比，血液、肺、脾、肾和脑组织中的细菌负荷减少。在 GBS 阴道定植的小鼠模型中，我们还观察到与野生型相比，缺失突变体更容易从阴道中清除。有趣的是，感染突变体的小鼠血清中发现的促炎细胞因子水平较低。我们的结果表明，LytSR TCS 在 GBS 组织侵袭和发病机制以及粘膜定植的持续存在中起着关键作用。
重要性
GBS 是女性泌尿生殖道的常见共生菌，也是世界卫生组织优先病原体之一。该细菌已经进化出适应和在其宿主中生存的机制，其中许多机制是通过双组分信号转导系统（TCS）调节的；然而，TCS 对 GBS 致病性的确切贡献在很大程度上仍然不清楚。我们构建了一个 CC-17 高毒力 GBS 临床分离株中 TCS 缺失突变体。使用小鼠模型，我们表明 LytSR 调节系统通过促进生物膜形成对于阴道定植是必不可少的。我们还观察到缺乏导致毒力特性显著减弱，血液中促炎细胞因子水平降低。我们的研究结果具有重要意义，因为它们揭示了 LytSR 在 GBS 中以前未报道的作用，并为更好地理解其从无害共生菌转变为致命病原体的能力铺平了道路。
