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Review
. 2013 Mar;15(3):395-402.
doi: 10.1111/cmi.12063. Epub 2012 Dec 2.

Autophagy and bacterial clearance: a not so clear picture

Serge Mostowy  1
Affiliations
Free PMC article
Review

Autophagy and bacterial clearance: a not so clear picture

Serge Mostowy. Cell Microbiol. 2013 Mar.
Free PMC article

Abstract

Autophagy, an intracellular degradation process highly conserved from yeast to humans, is viewed as an important defence mechanism to clear intracellular bacteria. However, recent work has shown that autophagy may have different roles during different bacterial infections that restrict bacterial replication (antibacterial autophagy), act in cell autonomous signalling (non-bacterial autophagy) or support bacterial replication (pro-bacterial autophagy). This review will focus on newfound interactions of autophagy and pathogenic bacteria, highlighting that, in addition to delivering bacteria to the lysosome, autophagy responding to bacterial invasion may have a much broader role in mediating disease outcome.

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Figures

Fig. 1
Fig. 1
Different autophagy pathways triggered by bacterial invasion. A. Antibacterial autophagy. After entry into host cells, bacteria are localized inside an internalization vacuole. Upon vacuolar disruption, autophagy may recognize ubiquitination signals and intracellular pathogens located (left) in the cytosol (e.g. L. monocytogenes, S. flexneri, S. Typhimurium) and (right) inside a damaged internalization vacuole (e.g. M. tuberculosis). In both cases, the enclosed bacterium is delivered to the lysosome for degradation. B. Non-bacterial autophagy. Autophagy may be _targeted against cellular disturbances arising from the bacterial invasion process, such as membrane damaged from bacterial entry or vacuolar disruption. (Left) Damaged membrane, and inflammasome components localized to damaged membrane, may be ubiquitinated and _targeted to autophagy. (Right) Damaged membrane can also be recognized for autophagy by non-ubiquitin signals (e.g. NDP52–galectin 8). In both cases, non-bacterial autophagy may trigger cell autonomous signalling and influence bacterial replication. C. Pro-bacterial autophagy. Some internalized bacteria (e.g. S. aureus, B. abortus) may recruit a subset of the autophagy machinery and create a replicative niche inside an autophagosome-like vacuole. These bacteria subvert the autophagy machinery to avoid degradation in a lysosomal compartment and support bacterial replication. Ub, ubiquitin; SLR, autophagy receptor (e.g. p62, NDP52); LC3, ATG8 family proteins.
Fig. 2
Fig. 2
The Shigella paradigm. Several autophagy pathways are recruited to S. flexneri, and autophagy (using non-mutually exclusive and parallel recognition events) may have different roles during Shigella infection. It will be important to identify unique markers for the different autophagy pathways triggered by Shigella, and to define their specific roles in pathogen clearance. A. EM image showing LC3-positive, double membrane surrounding cytosolic Shigella (Ogawa et al., 2005). B. TECPR1 (red) binds to ATG5 and localizes with LC3 (green) around cytosolic Shigella in the absence of ubiquitin (Ogawa et al., 2011). C. The septin cage (SEPT2, red) entraps cytosolic Shigella and _targets bacteria to autophagy (LC3, green) (Mostowy et al., 2010). D. Recruitment of the septin cage (SEPT2, red) to cytosolic Shigella is interdependent with recruitment of ubiquitin and autophagy receptors (p62, green) (Mostowy et al., 2010). E. NOD proteins (NOD2, green) and ATG16L1 (red) are recruited to the Shigella entry site and promote autophagy (Travassos et al., 2010). F. Galectin 3 (red), a marker for damaged membrane, localizes with autophagy receptors [p62 (here in cyan), NBR1 and NDP52] and LC3 (green) around Shigella (Dupont et al., ; Ligeon et al., 2011). G. Galectin 8 (green), a marker for damaged membrane, surrounding Shigella may recruit NDP52 in the absence of ubiquitin (Thurston et al., 2012). H. Membrane damage, labelled by NDP52 (green), around cytosolic Shigella causes intracellular amino acid starvation (Tattoli et al., 2012).
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