Fig. 1.

Microbial regulation of endocytosis. Microbial targeting of host endocytic pathways facilitates their invasion of host epithelial cells. Intracellular bacteria invade nonphagocytic host epithelial cells via one of two discrete mechanisms, both of which involve actin rearrangements due to activation of G proteins: zipper and trigger. Viruses exploit similar signaling pathways to facilitate actin rearrangements and invasion of host epithelial cells through three mechanisms: clathrin mediated, caveolar mediated, or macropinocytosis. Invasion of host epithelial cells by protozoa results following multiple complex interactions between the host and pathogen. As a result, protozoa invade host epithelial cells through multiple mechanisms. Trypanosoma cruzi invasion occurs as a result of either recruitment of lysosomes or phosphoinositide-3,4,5-triphosphate (PIP₃) to the site of invasion. Many extracellular bacteria produce protein toxins that directly modulate host cell signaling and endocytosis to actively remodel cellular physiology. Bacterial secretion systems directly inject bacterial toxins from the bacteria into the cytosol of host cells. Bacterial toxins secreted extracellularly contain domains that facilitate binding of host receptors and translocation across cellular membranes following endocytosis, or are delivered by outer membrane vesicles (OMVs). Many pathogens successfully evade host immune responses as a result of disrupting endocytic pathways. ER, endoplasmic reticulum; PI3K, phosphatidylinositol 3-kinase; CT, cholera toxin; CFTR, cystic fibrosis transmembrane conductance regulator; MHC I, major histocompatibility complex class I; eEF2, eukaryotic elongation factor-2; RSV, respiratory syncytial virus; ETA, exotoxin A; ETS, exoenzyme S; EE/RE, early endosome/recycling endosome; PKA, protein kinase A.