Xenophagy-Evasion Mechanisms by Intracellular Pathogens in Bacteria, Viruses, and Parasites

Autophagy is an essential process for maintaining cellular homeostasis. Xenophagy, a key defense mechanism, selectively degrades and eliminates pathogens such as bacteria, viruses, and parasites that have invaded the host. Host cells mark pathogens through ubiquitination. These marked pathogens are then recognized by autophagy receptors and sequestered within autophagosomes. The autophagosomes then fuse with lysosomes for degradation. However, many pathogens have evolved strategies to evade or suppress xenophagy at each step to survive the host defense system. This review outlines the molecular mechanisms of autophagy and summarizes recent research on how bacteria, viruses, and parasites evade xenophagy to cause disease. Pathogens utilize various proteins and mechanisms to do so, including removing ubiquitin chains, blocking access to autophagy receptors, and interfering with autophagosome formation and fusion. Understanding these host-pathogen interactions provides important clues for discovering new therapeutic targets for preventing and treating infectious diseases and for developing strategies to overcome drug resistance.