文献类型： 外文期刊

作者： Peng, Mingzheng ¹ ; Xu, Yuanyuan ³ ; Dou, Beibei ³ ; Yang, Fengming ³ ; He, Qiyun ³ ; Liu, Zewen ¹ ; Gao, Ting ¹ ; Liu, Wei ¹ ; Yang, Keli ¹ ; Guo, Rui ¹ ; Li, Chang ¹ ; Tian, Yongxiang ¹ ; Zhou, Danna ¹ ; Bei, Weicheng ² ; Yuan, Fangyan ¹ ;

作者机构： 1.Hubei Acad Agr Sci, Inst Anim Husb & Vet, Key Lab Prevent & Control Agents Anim Bacteriosis, Hubei Prov Key Lab Anim Pathogen Microbiol, Wuhan, Peoples R China

2.Hubei Hongshan Lab, Wuhan, Peoples R China

3.Huazhong Agr Univ, Coll Vet Med, Cooperat Innovat Ctr Sustainable Pig Prod, State Key Lab Agr Microbiol, Wuhan, Peoples R China

4.Guangxi Yangxiang Co Ltd, Guangxi, Peoples R China

关键词： Streptococcus suis; Zn uptake system; biofilm; drug resistance; virulence

期刊名称：MICROBIOLOGY SPECTRUM （ 影响因子：3.7； 五年影响因子：5.9 ）

ISSN： 2165-0497

年卷期： 2023 年 11 卷 3 期

页码：

收录情况： SCI

摘要： Streptococcus suis is an recognized zoonotic pathogen of swine and severely threatens human health. Zinc is the second most abundant transition metal in biological systems. Here, we investigated the contribution of zinc to the drug resistance and pathogenesis of S. suis. We knocked out the genes of AdcACB and Lmb, two Zn-binding lipoproteins. Compared to the wild-type strain, we found that the survival rate of this double-mutant strain (Delta adcA Delta lmb) was reduced in Zinc-limited medium, but not in Zinc-supplemented medium. Additionally, phenotypic experiments showed that the Delta adcA Delta lmb strain displayed impaired adhesion to and invasion of cells, biofilm formation, and tolerance of cell envelope-targeting antibiotics. In a murine infection model, deletion of the adcA and lmb genes in S. suis resulted in a significant decrease in strain virulence, including survival rate, tissue bacterial load, inflammatory cytokine levels, and histopathological damage. These findings show that AdcA and Lmb are important for biofilm formation, drug resistance, and virulence in S. suis.IMPORTANCE Transition metals are important micronutrients for bacterial growth. Zn is necessary for the catalytic activity and structural integrity of various metalloproteins involved in bacterial pathogenic processes. However, how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity remains unknown. Thus, pathogenic bacteria must acquire Zn during infection in order to successfully survive and multiply. The host uses nutritional immunity to limit the uptake of Zn by the invading bacteria. The bacterium uses a set of high-affinity Zn uptake systems to overcome this host metal restriction. Here, we identified two Zn uptake transporters in S. suis, AdcA and Lmb, by bioinformatics analysis and found that an adcA and lmb double-mutant strain could not grow in Zn-deficient medium and was more sensitive to cell envelope-targeting antibiotics. It is worth noting that the Zn uptake system is essential for biofilm formation, drug resistance, and virulence in S. suis. The Zn uptake system is expected to be a target for the development of novel antimicrobial therapies. Transition metals are important micronutrients for bacterial growth. Zn is necessary for the catalytic activity and structural integrity of various metalloproteins involved in bacterial pathogenic processes.