Abstract:
Bacterial DeoR family transcription regulators regulate multiple physiological processes. Little is known about the function of DeoR family regulators in streptococci. Here, we identified a novel DeoR family regulator, GlpR, from Streptococcus suis, a pathogen causing severe diseases in pigs and humans. GlpR was involved in glycerol utilization and exhibited specific signature residues at positions 30-31 (KV) which are crucial for DNA binding. Deletion of glpR (ΔglpR) showed a significant increase in relative growth rate in glycerol medium compared to the wild-type (WT) and complementary strains (CΔglpR). Employing RNA-seq analysis, β-galactosidase activity analysis, and electrophoretic mobility shift assay, we discovered that GlpR directly represses the expression of glycerol metabolism-related genes pflB2, pflA1, and fsaA, encoding pyruvate formate-lyase and its activating enzyme, and fructose-6-phosphate aldolase, respectively. Compared to WT and CΔglpR, ΔglpR showed a reduced survival rate under oxidative stress and in murine macrophages and attenuated virulence in mice. GlpR probably enhances oxidative stress resistance and virulence in S. suis by functioning as a glycerol metabolic repressor decreasing energy consumption. These findings contribute to a better understanding of S. suis pathogenesis and enrich our knowledge of the biological functions of DeoR family regulators in streptococci.
摘要:
细菌DeoR家族转录调节因子调节多个生理过程。关于DeoR家族调节剂在链球菌中的功能知之甚少。这里,我们确定了一个新的DeoR家族调节因子,GlpR,来自猪链球菌,在猪和人类中引起严重疾病的病原体。GlpR参与甘油利用,并在30-31位(KV)表现出对DNA结合至关重要的特异性特征残基。与野生型(WT)和互补菌株(CΔglpR)相比,glpR(ΔglpR)的缺失显示甘油培养基中的相对生长速率显着增加。采用RNA-seq分析,β-半乳糖苷酶活性分析,和电泳迁移率变化分析,我们发现GlpR直接抑制甘油代谢相关基因pflB2、pflA1和fsaA的表达,编码丙酮酸甲酸裂解酶及其活化酶,和果糖-6-磷酸醛缩酶,分别。与WT和CΔglpR相比,ΔglpR在氧化应激和鼠巨噬细胞中显示出降低的存活率,并且在小鼠中毒力减弱。GlpR可能通过充当甘油代谢阻遏物减少能量消耗而增强猪链球菌的氧化应激抗性和毒力。这些发现有助于更好地理解猪链球菌的发病机制,并丰富我们对链球菌中DeoR家族调节因子的生物学功能的了解。