Salmonella enterica serovar Enteritidis (S. Enteritidis; wild type (WT)) is a major cause of foodborne illness globally. The ability of this pathogen to survive stress inside and outside the host, such as encountering antimicrobial peptides and heat stress, determines the efficiency of enteric infection. These stressors concertedly trigger virulence factors encoded on Salmonella pathogenicity islands (SPIs). Although RpoS is a well-known central transcriptional stress and virulence regulator, functional information regarding the genes of the regulon is currently limited. Here, we identified SEN1538 as a conserved RpoS-regulated gene belonging to the KGG protein superfamily. We further assessed its role in pathogenic stress responses and virulence. When SEN1538 was deleted (Δ1538), the pathogen showed reduced survival during antimicrobial peptide introduction and heat stress at 55°C compared to WT. The mutant displayed 70% reduced invasion in the HCT116 colon epithelial cell line, 5-fold attenuated phagocytic survival in RAW264.7 cells, and downregulation of several SPI-1 and SPI-2 genes encoding the three secretion system apparatus and effector proteins. Δ1538 also showed decreased virulence compared to WT, demonstrated by its reduced bacterial counts in the feces, mLN, spleen, and cecum of C57BL/6 mice. Comparative transcriptomic analysis of Δ1538 against WT revealed 111 differentially regulated genes, 103 of which were downregulated (fold change ≤ -1.5, P < 0.05). The majority of these genes were in clusters for metabolism, transporters, and pathogenesis, driving pathogenic stress responses and virulence. SEN1538 is, therefore, an important virulence determinant contributing to the resilience of S. Enteritidis to stress factors during infection.

中文翻译：

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RpoS 调节的 SEN1538 基因促进对应激的抵抗力并影响肠炎沙门氏菌血清型肠炎毒力。

肠炎沙门氏菌肠炎血清型（S. Enteritidis；野生型（WT））是全球食源性疾病的主要原因。这种病原体在宿主内外应激（例如遇到抗菌肽和热应激）下生存的能力决定了肠道感染的效率。这些应激源协同触发沙门氏菌致病岛（SPI）上编码的毒力因子。尽管 RpoS 是众所周知的中央转录应激和毒力调节因子，但目前有关调节子基因的功能信息有限。在这里，我们将 SEN1538 鉴定为属于 KGG 蛋白超家族的保守 RpoS 调节基因。我们进一步评估了其在致病应激反应和毒力中的作用。当 SEN1538 被删除 (Δ1538) 时，与 WT 相比，病原体在抗菌肽引入和 55°C 热应激期间的存活率降低。该突变体在 HCT116 结肠上皮细胞系中的侵袭能力降低了 70%，在 RAW264.7 细胞中的吞噬细胞存活率降低了 5 倍，并且编码三种分泌系统装置和效应蛋白的多个 SPI-1 和 SPI-2 基因下调。与 WT 相比，Δ1538 的毒力也有所降低，这通过 C57BL/6 小鼠粪便、mLN、脾脏和盲肠中的细菌计数减少得到证明。Δ1538 与 WT 的比较转录组分析揭示了 111 个差异调节基因，其中 103 个基因下调（倍数变化 ≤ -1.5，P < 0.05）。这些基因大多数集中在代谢、转运蛋白和发病机制上，驱动致病应激反应和毒力。因此，SEN1538 是一个重要的毒力决定因素，有助于肠炎沙门氏菌在感染期间对应激因素的恢复能力。