Cronobacter sakazakii is an opportunistic foodborne bacterial pathogen that shows resistance to multiple stress conditions. The PhoP/PhoQ two component system is a key regulatory mechanism of stress response and virulence in various bacteria, but its role in C. sakazakii has not been thoroughly studied. In this study, we found the PhoP/PhoQ system in C. sakazakii ATCC BAA-894 enhanced bacterial growth in conditions with low Mg²⁺, acid pH, and the presence of polymyxin B. Moreover, the ΔphoPQ strain significantly reduced survival following exposure to heat, high osmotic pressure, oxidative or bile salts compared with WT strain. Furthermore, the RNA-seq analysis indicated that 1029 genes were upregulated and 979 genes were downregulated in ΔphoPQ strain. The bacterial secretion system, flagella assembly, beta-Lactam resistance and two-component system pathways were significantly downregulated, while the ABC transporters and microbial metabolism in diverse environments pathways were upregulated. qRT-PCR analysis further confirmed that twelve genes associated with stress tolerance were positively regulated by the PhoP/PhoQ system. Therefore, these findings suggest that the PhoP/PhoQ system is an important regulatory mechanism for C. sakazakii to resist various environmental stress.

Cronobacter sakazakii是一种机会性食源性细菌病原体，对多种压力条件具有抵抗力。PhoP/PhoQ 两组分系统是各种细菌应激反应和毒力的关键调控机制，但其在C. sakazakii 中的作用尚未得到彻底研究。在本研究中，我们发现C. sakazakii ATCC BAA-894 中的 PhoP/PhoQ 系统在低 Mg ²⁺、酸性 pH 和多粘菌素 B 存在的条件下增强了细菌生长。此外，Δ phoPQ与 WT 菌株相比，该菌株在暴露于热、高渗透压、氧化盐或胆汁盐后显着降低了存活率。此外，RNA-seq 分析表明 Δ phoPQ菌株中有 1029 个基因上调，979 个基因下调。细菌分泌系统、鞭毛组装、β-内酰胺抗性和双组分系统途径显着下调，而不同环境途径中的 ABC 转运蛋白和微生物代谢上调。qRT-PCR 分析进一步证实了与胁迫耐受相关的 12 个基因受到 PhoP/PhoQ 系统的正调控。因此，这些发现表明 PhoP/PhoQ 系统是C. sakazakii的重要调控机制 抵抗各种环境压力。