Abstract

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.

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