Avoidance and Subversion of Eukaryotic Homeostatic Autophagy Mechanisms by Bacterial Pathogens

Abstract

Autophagy is a lysosomal recycling process conserved in eukaryotes, which maintains cellular homeostasis during stress and starvation conditions by degrading and recycling proteins, lipids and carbohydrates, ultimately increasing nutrient availability. An additional function of autophagy, termed xenophagy, is to detect, capture and destroy invading microorganisms, such as viruses, bacteria and protozoa, providing autophagy with a role in innate immunity. Many intracellular pathogens have however developed mechanisms to avoid xenophagy, and have evolved strategies to take advantage of select autophagic processes to undergo their intracellular lifecycle. This review article will discuss the molecular mechanisms used by the intracellular bacterial pathogens Francisella spp. and Brucella spp. to manipulate components of the autophagic pathway, promoting cytosolic growth in the case of Francisella spp., and facilitating cellular egress and cell-to-cell spread in the case of Brucella spp. These examples highlight how successful, highly infectious bacterial pathogens avoid or subvert host autophagy mechanisms normally employed to maintain eukaryotic homeostasis.

Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death

“…The exposure of chlamydiae or their products appears to lead to an autophagic response that ultimately results in programmed cell death. Autophagy is typically a pro-survival strategy used to degrade damaged organelles or cytoplasmic pathogens (Miller, 2016; Winchell et al, 2016). However, there is also crosstalk between autophagy and apoptosis where autophagic processes can be linked to cell death (Maiuri et al, 2007).…”

Autophagy and innate immunity: Insights from invertebrate model organisms

“…Some of these questions are addressed in several excellent reviews on autophagy and infection. [6][7][8] Here, we summarize some of the insights gained from studies of D. melanogaster and C. elegans, 2 powerful model systems that have enabled important discoveries about how metazoans use autophagy to protect against microbial infections. We define 'microbe' as an entity that causes infection in D. melanogaster or C. elegans; specifically, viruses, bacteria, and eukaryotic single-celled organisms.…”

Brucella Melitensis 16M Regulates the Effect of AIR Domain on Inflammatory Factors, Autophagy, and Apoptosis in Mouse Macrophage through the ROS Signaling Pathway

“…In the late stage of the cycle, the replicative BCV (rBCV) derived from endoplasmic reticulum is converted into autophagic BCV (aBCV)[11]. This process requires the autophagy initiation protein Ulk-1, autophagy gene Beclin 1 , and Atg14L [12]; this shows that atypical and classical autophagy induced by Brucella share common upstream regulatory pathways[13]. Smooth Brucella inhibits macrophage apoptosis, while rough Brucella induces macrophage apoptosis[5].…”