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By repairing oxidized methionine (Met-SO) residues, methionine sulfoxide reductases (Msrs) play important role in survival and virulence of <i>Salmonella</i> Typhimurium (<i>S.</i> Typhimurium). <i>Salmonella</i> encodes five <i>msr</i>s. Through the generation of single and cumulative deletion mutants (Δ<i>msrA</i>, Δ<i>msrP</i>, Δ<i>msrAC</i>, Δ<i>msrACP</i>, Δ<i>msrACPB</i>, and Δ<i>msrACPBbisC</i>), we analyzed the relative contribution of various <i>msr</i> genes (<i>msrA</i>, <i>msrB</i>, <i>msrC</i>, <i>msrP</i>, and <i>bisC</i>) in oxidative stress survival of <i>S. </i>Typhimurium. We evaluated the effects of <i>msr</i> gene deletion(s) on protein oxidation, survival in immune cells, colonization in poultry organs, and immune responses. The mutant strains exhibited elevated levels of protein aggregation, with the ∆<i>msrACPBbisC</i> strain accumulating the highest levels of protein aggregates. Survival assays in macrophages and dendritic cells demonstrated that the <i>msrA</i>, <i>msrC</i>, and <i>bisC</i> genes play critical roles in proliferation in immune cells, whereas the contribution of <i>msrP</i> is minimal. Mutants are defective in cecal colonization and systemic dissemination to the spleen and liver, the degree of which depends on the number of mutations. One-day-old female White Leghorn chicks were inoculated with <i>msr</i> mutant strains showed modulated humoral as well as cellular immune responses as compared to <i>S. </i>Typhimurium infected counterpart. These findings underscore the critical roles of <i>msr</i> genes in colonization in poultry and modulation of immune responses, and have implications in the design and development of live vaccines against <i>S.</i> Typhimurium for poultry.

甲硫氨酸亚砜还原酶（methionine sulfoxide reductases, Msrs）可通过修复氧化型甲硫氨酸（Met-SO）残基，在鼠伤寒沙门氏菌（Salmonella Typhimurium，S. Typhimurium）的存活与致病力中发挥重要作用。鼠伤寒沙门氏菌基因组编码5个msr基因。本研究通过构建单基因及多基因累积缺失突变株（ΔmsrA、ΔmsrP、ΔmsrAC、ΔmsrACP、ΔmsrACPB及ΔmsrACPBbisC），分析了各类msr基因（msrA、msrB、msrC、msrP及bisC）在鼠伤寒沙门氏菌氧化应激存活中的相对贡献。本研究评估了msr基因缺失对蛋白质氧化水平、免疫细胞内存活、家禽器官定植以及免疫应答的影响。结果显示，突变菌株的蛋白质聚集水平显著升高，其中ΔmsrACPBbisC菌株的蛋白质聚集体积累量最高。巨噬细胞与树突状细胞内的存活实验表明，msrA、msrC及bisC基因在免疫细胞增殖过程中发挥关键作用，而msrP的贡献则相对微弱。突变株在盲肠定植以及向脾脏、肝脏的全身播散中存在缺陷，其缺陷程度取决于所携带的突变数量。将msr突变株接种1日龄雌性白来航鸡雏后，相较于感染野生型鼠伤寒沙门氏菌的对照组，受试鸡的体液免疫与细胞免疫应答均发生显著调控变化。本研究结果凸显了msr基因在家禽宿主定植与免疫应答调控中的关键作用，可为针对家禽鼠伤寒沙门氏菌的减毒活疫苗的设计与开发提供重要参考依据。