Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
Cell Host Microbe. 2018 Jan 10;23(1):65-76.e6. doi: 10.1016/j.chom.2017.12.001.
Salmonella Typhi is the cause of typhoid fever, a major global health concern. An essential virulence factor of this pathogen is typhoid toxin. In contrast to most AB-type toxins, typhoid toxin is exclusively expressed by intracellular bacteria. The regulatory networks that ensure this unique gene expression pattern are unknown. Here, we developed FAST-INSeq, a genome-wide screening approach to identify S. Typhi genes required for typhoid toxin expression within infected cells. We find that typhoid toxin expression is controlled by a silencing and counter-silencing mechanism through the opposing actions of the PhoP/PhoQ two-component regulatory system and the histone-like protein H-NS. The screen also identified bacterial mutants that alter the proportion of intracellular S. Typhi that reside within an intravacuolar environment, which was essential for toxin expression. Collectively, these data describe a regulatory mechanism that allows a bacterial pathogen to exclusively express a virulence factor when located within a specific intracellular compartment.
伤寒沙门氏菌是伤寒的病原体，是全球主要的健康关注点之一。这种病原体的一个重要毒力因子是伤寒毒素。与大多数 AB 型毒素不同，伤寒毒素仅由细胞内细菌表达。确保这种独特基因表达模式的调控网络尚不清楚。在这里，我们开发了 FAST-INSeq，这是一种全基因组筛选方法，用于鉴定感染细胞中表达伤寒毒素所需的伤寒沙门氏菌基因。我们发现，伤寒毒素的表达受沉默和反沉默机制的控制，该机制通过 PhoP/PhoQ 双组分调控系统和组蛋白样蛋白 H-NS 的相反作用来实现。该筛选还鉴定了细菌突变体，这些突变体改变了胞内伤寒沙门氏菌位于细胞内小泡环境中的比例，这对于毒素表达至关重要。总的来说，这些数据描述了一种调控机制，使细菌病原体在位于特定细胞内隔室时能够特异性表达一种毒力因子。
