An inside job: subversion of the host secretory pathway by intestinal pathogens

The cellular secretory pathway, composed of the endoplasmic reticulum, Golgi apparatus, and cellular vesicles, mediates the intracellular trafficking of proteins and lipids. Gastrointestinal pathogens frequently affect the functions of enterocytes, the differentiated cells involved in secretion and absorption of extracellular molecules. Microbial pathogenesis can be enhanced by altering the trafficking of key molecules such as brush border enzymes, soluble immune mediators such as cytokines and chemokines, and MHC Class I molecules, all of which rely on the secretory pathway for their appropriate cellular localization. This review focuses on our current understanding of the distinct mechanisms employed by enteric pathogens to antagonize the secretory pathway.

Many pathogens encode individual or multiple proteins to antagonize the secretory pathway, including disrupting the trafficking of vesicles between the endoplasmic reticulum, Golgi, and plasma membrane. This antagonism allows for increased pathogenesis and can assist, directly or indirectly, in microbial replication. Virtually all arms of the secretory pathway are targeted by intestinal pathogens, supporting the pathogenic significance of shutting this pathway down.

This review summarizes the mechanisms utilized by gut pathogens to disrupt the cellular secretory pathway and addresses potential therapeutic targets to combat these highly prevalent and burdensome microbes.