YggG is a Novel SPI-1 Effector Essential for Salmonella Virulence

Abstract

Salmonella is a leading cause of food borne illness and poses a major public health problem worldwide. Two type III secretion systems (TTSSs) are responsible for the delivery of a series of bacterial effectors into the infected cells to reprogram host cell functions to promote bacterial invasion and intracellular survival/replication. Nearly half of Salmonella genes encode proteins that are annotated as \"hypothetical\". We hypothesize that some of these hypothetical proteins might be TTSS effectors and participate in Salmonella virulence. In this study, we employed an in silico screen to identify putative TTSS effector proteins and performed a large scale screening of Salmonella effectors using a {beta}-lactamase protein translocation reporter assay. We identified 22 novel effectors that have not been previously reported. One of the effector - YggG, is found to be cytotoxic to mammalian cells when overexpressed suggesting interference with mammalian cell functions and survival. Importantly, Salmonella strains lacking YggG has reduced virulence in the mouse infection model. Our study demonstrated that YggG and its protease activity are required for Salmonella virulence in the mouse infection model. Surprisingly, no detectable roles in invasion into epithelial cells and no effect on the survival and replication inside cultured macrophages. We speculate that YggG may be involved in altering some aspects of the host immune system to promote infection. Our finding significantly expands the number of known Salmonella effectors, and laid a solid foundation in further understanding Salmonella pathogenesis.\n\nAbstract ImportanceSalmonellosis continues to be public health concern in the USA and the world. Salmonella delivers a set of bacterial proteins (effectors) into the host cells to invade non-phagocytic cells and to replicate inside the infected cells. Identification and characterization of these effectors are pivotal to the understanding of how Salmonella causes diseases. In addition, Nearly half of Salmonella genes encode proteins that are annotated as \"hypothetical\". We have identified 22 novel effectors that have not been previously reported. Our finding significantly expands the number of known Salmonella effectors, and laid a solid foundation in further understanding Salmonella pathogenesis.