Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

Trends Mol Med. 2016 Dec;22(12):1060-1076. doi: 10.1016/j.molmed.2016.10.008. Epub 2016 Nov 17.

Abstract

Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis. In light of current efforts to manipulate autophagy and the development of host-directed therapies to fight bacterial infections, we also discuss the implications stemming from the complicated relationship that exists between autophagy and bacterial pathogens.

Keywords: Mycobacterium tuberculosis; autophagy; bacterial pathogens; host-directed therapies; xenophagy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Autophagy* / drug effects
  • Autophagy-Related Proteins / immunology
  • Bacteria / immunology*
  • Bacterial Infections / drug therapy
  • Bacterial Infections / immunology*
  • Bacterial Infections / pathology
  • Bacterial Physiological Phenomena
  • Drug Discovery
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate*
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / physiology
  • Tuberculosis / drug therapy
  • Tuberculosis / immunology
  • Tuberculosis / pathology

Substances

  • Anti-Bacterial Agents
  • Autophagy-Related Proteins