Peng Wei, Yang Xia, Wang Yanna, Wang Ningning, Li Xiaoyue, Chen Huanchun, Yuan Fangyan, Bei Weicheng
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China.
Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture), Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan, China.
Vet Microbiol. 2022 Sep;272:109518. doi: 10.1016/j.vetmic.2022.109518. Epub 2022 Jul 28.
Manganese (Mn) is an important micronutrient that is not readily available to pathogens during infection. Hosts resist the invasion of pathogens through nutritional immunity and oxidative stress. To overcome this nutrient restriction, bacteria utilize high affinity transporters to compete with nutrient-binding proteins (e.g., calprotectin). Little is known about the role of Mn in the pathophysiology of Streptococcus suis. Here, we revealed that the tolerance of S. suis to calprotectin and oxidative stress was associated with Mn. Inactivation of Mn uptake system, TroABCD, in S. suis decreased the tolerance to calprotectin and oxidative stress. Furthermore, Mn uptake system mutant strains reduced capacity for bacterial cellular survival, and attenuated virulence in a mouse model. To explore the regulatory mechanism, we determined the transcriptional start site of troABCD using capping rapid amplification of cDNA ends. Furthermore, we revealed that TroR was a transcriptional regulatory repressor of troABCD. In the absence of troR, transcription levels of troA, troB, troC, and troD were not inhibited by low or high Mn levels, and intracellular Mn contents of mutant strains were higher than that of the wild-type strain. Finally, we used electrophoretic mobility shift assay to demonstrate that TroR bound the promoter region of troABCD. Collectively, this study revealed that Mn acquisition was essential for pathogenesis of S. suis and Mn uptake systems should be targets for the development of new antimicrobials.
锰（Mn）是一种重要的微量营养素，在感染期间病原体难以获取。宿主通过营养免疫和氧化应激来抵抗病原体的入侵。为了克服这种营养限制，细菌利用高亲和力转运蛋白与营养结合蛋白（如钙卫蛋白）竞争。关于锰在猪链球菌病理生理学中的作用知之甚少。在这里，我们发现猪链球菌对钙卫蛋白和氧化应激的耐受性与锰有关。猪链球菌中锰摄取系统TroABCD的失活降低了对钙卫蛋白和氧化应激的耐受性。此外，锰摄取系统突变株降低了细菌细胞存活能力，并在小鼠模型中减弱了毒力。为了探索调控机制，我们使用cDNA末端快速扩增技术确定了troABCD的转录起始位点。此外，我们发现TroR是troABCD的转录调节阻遏物。在没有troR的情况下，troA、troB、troC和troD的转录水平不受低锰或高锰水平的抑制，突变株的细胞内锰含量高于野生型菌株。最后，我们使用电泳迁移率变动分析来证明TroR结合troABCD的启动子区域。总的来说，这项研究表明锰的获取对猪链球菌的致病机制至关重要，锰摄取系统应成为新型抗菌药物开发的靶点。
