New Roles for Two-Component System Response Regulators of Salmonella enterica Serovar Typhi during Host Cell Interactions

In order to survive external stresses, bacteria need to adapt quickly to changes in their environment. One adaptive mechanism is to coordinate and alter their gene expression by using two-component systems (TCS). TCS are composed of a sensor kinase that activates a transcriptional response regulator by phosphorylation. TCS are involved in motility, virulence, nutrient acquisition, and envelope stress in many bacteria. The pathogenic bacteria serovar Typhi ( Typhi) possess 30 TCSs, is specific to humans, and causes typhoid fever. Here, we have individually deleted each of the 30 response regulators. We have determined their role during interaction with host cells (epithelial cells and macrophages). Deletion of most of the systems (24 out of 30) resulted in a significant change during infection. We have identified 32 new phenotypes associated with TCS of Typhi. Some previously known phenotypes associated with TCSs in were also confirmed. We have also uncovered phenotypic divergence between serovars, as distinct phenotypes between Typhi and Typhimurium were identified for . This finding highlights the importance of specifically studying Typhi to understand its pathogenesis mechanisms and to develop strategies to potentially reduce typhoid infections.