Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

ABSTRACT: Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi (S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at th

SUBMITTER: Alvarez MI 

PROVIDER: S-EPMC5604016 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature