Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, China.
J Bacteriol. 2021 May 20;203(12):e0012721. doi: 10.1128/JB.00127-21. Epub 2021 Apr 5.
The intracellular bacterial pathogen causes persistent infections in various mammalian species. To survive and replicate within macrophages, these bacteria must be able to withstand oxidative stresses and express the type IV secretion system (T4SS) to evade host immune responses. The extracytoplasmic function (ECF) sigma factor system is a major signal transduction mechanism in bacteria that senses environmental cues and responds by regulating gene expression. In this study, we defined an ECF σ and its cognate anti-σ factor in Brucella melitensis M28 by conserved domain analysis and a protein interaction assay. BcrS directly activates an adjacent operon, , that encodes a methionine-rich peptide and a putative methionine sulfoxide reductase system, whereas AbcS is a negative regulator of and . The - and operons can be induced by hypochlorous acid and contribute to hypochlorous acid resistance . Next, RNA sequencing analysis and genome-wide recognition sequence search identified the regulons of BcrS and AbcS. Interestingly, we found that BcrS positively influences T4SS expression in an AbcS-dependent manner and that AbcS also affects T4SS expression independently of BcrS. Last, we demonstrate that is required for the maintenance of persistent infection, while is dispensable in a mouse infection model. Collectively, we conclude that BcrS and AbcS influence expression of multiple genes responsible for virulence traits. is a notorious intracellular pathogen that induces chronic infections in animals and humans. To survive and replicate within macrophages, these bacteria require a capacity to withstand oxidative stresses and to express the type IV secretion system (T4SS) to combat host immune responses. In this study, we characterized an extracytoplasmic function sigma/anti-sigma factor system that regulates resistance to reactive chlorine species and T4SS expression, thereby establishing a potential link between two crucial virulence traits of . Furthermore, the anti-sigma factor AbcS contributes to persistent infection of mice. Thus, this work provides novel insights into virulence regulation as well as a potential drug target for fighting infections.
胞内细菌病原体 可在多种哺乳动物物种中引发持续性感染。为了在巨噬细胞内存活和复制，这些细菌必须能够承受氧化应激，并表达 IV 型分泌系统（T4SS）以逃避宿主免疫反应。胞外功能（ECF）σ因子系统是细菌中主要的信号转导机制，可感知环境线索，并通过调节基因表达做出响应。在这项研究中，我们通过保守结构域分析和蛋白质相互作用测定，在布鲁氏菌 M28 中定义了一个 ECF σ 及其同源抗-σ 因子 。BcrS 直接激活相邻的操纵子 ，该操纵子编码富含甲硫氨酸的肽和一种假定的甲硫氨酸亚砜还原酶系统，而 AbcS 是 和 的负调控因子。 和 操纵子可被次氯酸诱导，并有助于次氯酸抗性 。接下来，RNA 测序分析和全基因组识别序列搜索鉴定了 BcrS 和 AbcS 的调控子。有趣的是，我们发现 BcrS 以 AbcS 依赖的方式正向影响 T4SS 表达，而 AbcS 也独立于 BcrS 影响 T4SS 表达。最后，我们证明 在维持持续性感染中是必需的，而 在小鼠感染模型中是可有可无的。总之，我们得出结论，BcrS 和 AbcS 影响负责毒力特征的多个基因的表达。 是一种臭名昭著的胞内病原体，可在动物和人类中引发慢性感染。为了在巨噬细胞内存活和复制，这些细菌需要具备承受氧化应激的能力，并表达 IV 型分泌系统（T4SS）以对抗宿主免疫反应。在这项研究中，我们描述了一个调节对活性氯物种的抗性和 T4SS 表达的胞外功能 σ/抗-σ 因子系统，从而在 两种关键毒力特征之间建立了潜在联系。此外，抗-σ 因子 AbcS 有助于 对小鼠的持续性感染。因此，这项工作为 毒力调控提供了新的见解，并为抗击 感染提供了一个潜在的药物靶点。
