Pathways of host cell exit by intracellular pathogens.

Antje Flieger,Gabriele Pradel,Mathias W Hornef,Freddy Frischknecht,Georg Haecker

doi:10.15698/mic2018.12.659

Antje Flieger, Gabriele Pradel + Show 3 more

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https://doi.org/10.15698/mic2018.12.659

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Abstract

Host cell exit is a critical step in the life-cycle of intracellular pathogens, intimately linked to barrier penetration, tissue dissemination, inflammation, and pathogen transmission. Like cell invasion and intracellular survival, host cell exit represents a well-regulated program that has evolved during host-pathogen co-evolution and that relies on the dynamic and intricate interplay between multiple host and microbial factors. Three distinct pathways of host cell exit have been identified that are employed by three different taxa of intracellular pathogens, bacteria, fungi and protozoa, namely (i) the initiation of programmed cell death, (ii) the active breaching of host cellderived membranes, and (iii) the induced membrane-dependent exit without host cell lysis. Strikingly, an increasing number of studies show that the majority of intracellular pathogens utilize more than one of these strategies, dependent on life-cycle stage, environmental factors and/or host cell type. This review summarizes the diverse exit strategies of intracellular-living bacterial, fungal and protozoan pathogens and discusses the convergently evolved commonalities as well as system-specific variations thereof. Key microbial molecules involved in host cell exit are highlighted and discussed as potential targets for future interventional approaches.

Highlights

Infectious diseases caused by viruses, bacteria, fungi, or parasites still represent a major cause of morbidity worldwide and account for almost 50,000 deaths every day [1]
Three distinct pathways of host cell exit have been identified that are employed by three different taxa of intracellular pathogens, bacteria, fungi and protozoa, namely (i) the initiation of programmed cell death, (ii) the active breaching of host cellderived membranes, and (iii) the induced membrane-dependent exit without host cell lysis
This review summarizes the diverse exit strategies of intracellular-living bacterial, fungal and protozoan pathogens and discusses the convergently evolved commonalities as well as system-specific variations thereof

Summary

Introduction

Infectious diseases caused by viruses, bacteria, fungi, or parasites still represent a major cause of morbidity worldwide and account for almost 50,000 deaths every day [1]. EXIT PATHWAYS Current data indicate that at least three principal exit pathways are used by intracellular pathogens (outlined in Fig. 1) (reviewed in [3,4,5,6,7]): (i) PCD including the non-lytic apoptosis and the lytic necroptosis and pyroptosis pathways, employed by bacterial, fungal and protozoan pathogens; (ii) the active breaching of host cell-derived membranes such as the endosomal, the vacuolar and/or the host cell plasma membrane, as shown for a variety of bacterial and protozoan parasites; (iii) the induced membranedependent exit without host cell lysis, e.g. via actin-based protrusions, extrusions, budding, exocytosis, expulsion or ejection, as has been demonstrated for some bacteria, for the yeast Cryptococcus and for Plasmodium.

Results

Conclusion