Characterization of the yehUT Two-Component Regulatory System of Salmonella enterica Serovar Typhi and Typhimurium

Proteins exhibiting hyper-variable sequences within a bacterial pathogen may be associated with host adaptation. Several lineages of the monophyletic pathogen Salmonella enterica serovar Typhi (S. Typhi) have accumulated non-synonymous mutations in the putative two-component regulatory system yehUT. Consequently we evaluated the function of yehUT in S. Typhi BRD948 and S. Typhimurium ST4/74. Transcriptome analysis identified the cstA gene, encoding a carbon starvation protein as the predominantly yehUT regulated gene in both these serovars. Deletion of yehUT had no detectable effect on the ability of these mutant Salmonella to invade cultured epithelial cells (S. Typhi and S. Typhimurium) or induce colitis in a murine model (S. Typhimurium only). Growth, metabolic and antimicrobial susceptibility tests identified no obvious influences of yehUT on these phenotypes.

细菌病原体中具有高变序列（hyper-variable sequences）的蛋白质可能与宿主适应性相关。单系致病菌（monophyletic pathogen）肠炎沙门氏菌血清型伤寒沙门氏菌（Salmonella enterica serovar Typhi, S. Typhi）的多个谱系在推定的双组分调控系统（two-component regulatory system）yehUT中积累了非同义突变（non-synonymous mutations）。据此，我们对伤寒沙门氏菌BRD948与鼠伤寒沙门氏菌ST4/74中的yehUT功能进行了评估。转录组分析（transcriptome analysis）显示，编码碳饥饿蛋白（carbon starvation protein）的cstA基因是这两种血清型中主要受yehUT调控的基因。yehUT基因缺失对这些突变沙门氏菌侵袭培养上皮细胞（epithelial cells）的能力（伤寒沙门氏菌与鼠伤寒沙门氏菌），或在小鼠模型（murine model）中诱发结肠炎（colitis）的能力（仅鼠伤寒沙门氏菌）均无可检测到的显著影响。生长、代谢与抗菌敏感性试验（antimicrobial susceptibility tests）均未发现yehUT对上述表型存在明显影响。