Pseudogenes are accumulated in host-restricted Salmonella enterica serovars, while pseudogenization is primarily regarded as a process that purges unnecessary genes from the genome. Here we showed that the inactivation of sopA, which encodes an effector of Salmonella Pathogenicity Island 1, in human-restricted S. enterica serovar Typhi (S. Ty) and Paratyphi A (S. PA) is under positive selection and aimed to reduce bacterial cytotoxicity toward host macrophages. Moreover, we found that the expression of sopA in Salmonella Typhimurium (S. Tm), a broad-host-range serovar which causes systemic disease in mice, was negatively regulated during mice infection and survival in murine macrophages. The sopA repression in S. Tm is mediated by IsrM, a small RNA absent from the genome of S. Ty and S. PA. Due to the lack of IsrM, sopA expression was unregulated in S. Ty and S. PA, which might have facilitated the convergent inactivation of sopA in these two serovars. In conclusion, our findings demonstrate that sopA inactivation or intracellular repression is the target of positive selection during the systemic infection caused by S. enterica serovars.

假基因在宿主限制性肠道沙门氏菌血清型中积累，而假基因化主要被认为是从基因组中清除不必要基因的过程。在这里，我们表明，sopA的失活，编码沙门氏菌致病岛 1的效应子，在人类限制性S. enterica血清型伤寒 ( S. Ty) 和副伤寒 A ( S. PA) 中处于正选择状态，旨在减少细菌对宿主巨噬细胞的细胞毒性。此外，我们发现sopA在鼠伤寒沙门氏菌（S.Tm) 是一种广泛宿主范围的血清型，可引起小鼠全身性疾病，在小鼠感染和小鼠巨噬细胞存活期间受到负调控。S. Tm 中的sopA抑制由 IsrM 介导，IsrM 是S. Ty 和S. PA基因组中不存在的小 RNA 。由于缺乏 IsrM，S. Ty 和S. PA 中的sopA表达不受调节，这可能促进了这两个血清型中sopA的收敛失活。总之，我们的研究结果表明，sopA失活或细胞内抑制是由S. enterica血清型。