The role of glutathione for oxidative stress and pathogenicity of Streptococcus suis

Streptococcus suis is an important zoonotic pathogen that threatens human and pig health. During infection, the host can impose oxidative stress to resist pathogen invasion. Resistance to oxidative toxicity is an important factor for pathogens. Glutathione synthesis contributes to reactive oxygen species (ROS) detoxification in bacterial cells. Little is known about the roles of glutathione synthesis and transport in S. suis. In this study, we demonstrated that glutathione treatment increased oxidative stress tolerance in S. suis. GshAB and GshT were found in S. suis glutathione synthesis and import by bioinformatics. In vitro, inactivation of gshAB and gshT led to increased sensitivity to oxidative stress. Inactivation of gshT led to growth defects in the medium. The intracellular glutathione content of gshAB or gshT deletion mutants was lower than that of wild type (WT) strain. The phagocytic resistance of gshAB and gshT mutants was lower than that of the WT strain. Moreover, the virulence of gshAB and gshT deletion mutants was significantly lower than that of the WT strain in mouse survival and tissue loading experiments. In conclusion, these results revealed the functions of GshAB and GshT in the pathogenesis of S. suis. These findings enhance our understanding of bacterial virulence mechanisms and may provide a new avenue for therapeutic intervention aimed at curbing S. suis infections.猪链球菌（Streptococcus suis, S. suis）是一种重要的人畜共患病原菌，可威胁人类与生猪的健康。在病原菌感染宿主的过程中，宿主会通过激活氧化应激通路抵御其入侵，而抗氧化毒性能力是病原菌成功定植与致病的关键因素之一。谷胱甘肽合成可介导细菌细胞内活性氧（reactive oxygen species, ROS）的解毒过程。目前学界对猪链球菌谷胱甘肽合成与转运的功能尚缺乏深入了解。本研究证实，谷胱甘肽处理可提升猪链球菌的氧化应激耐受能力。通过生物信息学分析，我们在猪链球菌中鉴定出参与谷胱甘肽合成与摄取的GshAB与GshT蛋白。体外实验结果显示，敲除gshAB与gshT会使菌株对氧化应激的敏感性显著升高；单独敲除gshT还会导致菌株在培养基中出现生长缺陷。gshAB或gshT缺失突变株的胞内谷胱甘肽含量均低于野生型（wild type, WT）菌株。上述突变株的吞噬抵抗能力也显著弱于野生型菌株。此外，在小鼠存活实验与组织载菌量实验中，gshAB和gshT缺失突变株的毒力均显著低于野生型菌株。综上，本研究揭示了GshAB与GshT在猪链球菌致病过程中的核心功能。上述发现加深了我们对细菌毒力机制的理解，或可为遏制猪链球菌感染的治疗干预提供全新研究方向。