Cellular autophagy: surrender, avoidance and subversion by microorganisms

Key Points

• Autophagy is an evolutionarily conserved cellular process that is initiated by starvation and other developmental and environmental cues. The formation and maturation of autophagosomes involves the sequestration of cytoplasm within double-membrane-bound vesicles and leads to proteasome-independent degradation of the cytosolic contents.

• Many genes that are required for autophagy have been identified, first in the yeast Saccharomyces cerevisiae, and then in other organisms by homology.

• Numerous microscopical, pharmacological and biochemical assays for autophagy have been developed. The identification of genes that are required for autophagy now allows genetic tests for the involvement of autophagy in a process of interest.

• Several invasive bacterial species are vulnerable to destruction by autophagy. However, it has been argued that Legionella pneumophila and several other bacterial species can subvert autophagic components to enhance their growth.

• One of the consequences of the activation of the antiviral protein PKR is an increase in cellular autophagy, which makes it likely that autophagy is a component of the cellular antiviral response. However, several positive-strand RNA viruses replicate their genomes on double-membrane-bound vesicles that are thought to be derived from autophagic structures.

• As for other cellular defences against microorganisms, some bacteria and viruses seem to have evolved mechanisms to inhibit or subvert autophagy.

Abstract

Intracellular bacteria and viruses must survive the vigorous antimicrobial responses of their hosts to replicate successfully. The cellular process of autophagy — in which compartments bound by double membranes engulf portions of the cytosol and then mature to degrade their cytoplasmic contents — is likely to be one such host-cell response. Several lines of evidence show that both bacteria and viruses are vulnerable to autophagic destruction and that successful pathogens have evolved strategies to avoid autophagy, or to actively subvert its components, to promote their own replication. The molecular mechanisms of the avoidance and subversion of autophagy by microorganisms will be the subject of much future research, not only to study their roles in the replication of these microorganisms, but also because they will provide — as bacteria and viruses so often have — unique tools to study the cellular process itself.