Table 1.

Pathogens associated with the autophagic machinery

Bacteria	Autophagic machinery	Description	References
Mycobacterium Tuberculosis (Mtb)	ATG5, miRNA125a	Induction of autophagy promotes clearance; unique role for ATG5, but not other autophagy proteins, in PMN during infection in vivo	[20, 21, 47, 75]
		MtB infection elevates expression of miRNA-125a-3p (miR-125a) and targets UVRAG to inhibit autophagy and phagosomal maturation
Mycobacterium bovis	ATG5	Induction of autophagy promotes clearance	[20, 75]
Burkholderia pseudomallei	LC3	LAP required for clearance	[76, 77]
		Bacterial Bsa T3SS effector proteins, bopA and bipD, increases bacterial survival by decreasing LC3 accumulation
Group A Streptococcus (GAS)	ATG5, NDP52, p62, NDR1	LC3 decorated autophagosome containing SpeB cysteine protease degrades the ubiquitin-LC3 adaptor proteins NDP52, p62, and NDR1	[17, 20, 77, 78]
Listeria monocytogenes	p62, ATG5, Rubicon	Macroautophagy and LAP induced; mediates inflammatory responses to pathogen	[58, 79, 80]
		LLO blocks maturation of autophagosome and evades into cytosol by releasing ActA
Bacteroides fragilis	ATG16L1, Rubicon	Outer membrane vesicles (OMVs) activate LAP for protection from colitis	[52]
Salmonella enterica serovar Typhimurium	NDP52, TBK1, OPTN, ATG9, ATG16L1	Delivery of ubiquitinated bacteria or bacterial substrates for degradation	[28, 37]
Shigella flexneri	ATG5, NBR1, NDP52	Secretes VirG which binds to ATG5 and activates autophagy; delivery of ubiquitinated bacteria or bacterial substrates for degradation	[19, 77, 80]
		IcsB secreted by Shigella competes with ATG5
Legionella pneumophila	Beclin 1, LC3	Inhibition of Beclin 1 restricts autophagosome initiation and elongation.	[17, 81, 82]
		RavZ and LegA9 secreted from T4SS uncouples LC3 from autophagosome membrane and inhibits autophagosome elongation and maturation.
		L. pneumophila secretes effector protein, SGPL1 targets host sphingolipid metabolism, inhibit autophagosome formation and causes starvation-induced autophagy for intracellular survival
Adherent & invasive Escherichia coli (AIEC)	ULK1, LC3	HIF1α-mediated retention in LC3-II+ vesicles and induces phosphorylation of ULK1	[83]
Uropathogenic E. coli	ATG16L1	Required for clearance	[84]
Yersinia Pseudotubercul osis	ATG5	Defect in acidification of the LC3+ autophagosome-like vacuoles containing pathogen.	[17, 20]
Yersinia pestis	LC3	Resides in LC3+ vesicles, yet prevents vacuole acidification	[17, 85]
Citrobacter rodentium	ATG16L1	Required for clearance	[86]
Pseudomonas aeruginosa	ATG7, Beclin 1	Autophagy mediated clearance	[87]
Klebsiella pneumoniae	ATG7	Autophagy mediated clearance	[88]
Franscisella tularensis	NOX2, Beclin 1, ATG5, ATG12, ATG16L, ATG7, ATG4	Disruption of NOX2-mediated ROS; downregulation of autophagy genes	[89]
Coxiella burnetii	Varies	Recruits autophagosomes to acquire nutrients or other factors that may trigger differentiation, and delays fusion with lysosomes for viral replication	[90, 91]
Brucella abortus	ULK1, Beclin 1, ATG14, VPS34	Selectively recruits autophagy proteins to subvert clearance	[48, 49]
Viruses	Autophagic machinery	Description	References
HBV	Rubicon, ATG5	Rubicon reduces IFN production and binds to NEMO to suppress ubiquitination, delays autophagosome maturation and allows viral replication; autophagy inhibits viral clearance	[64]
VSV	Rubicon, ATG5, ATG12	Rubicon reduces IFN production and binds to NEMO to suppress ubiquitination and allows viral replication; autophagy inhibits antiviral response	[63, 64, 92]
IAV	Beclin 1, Rubicon	Influenza virus matrix protein 2 causes inhibition of beclin1 restricts autophagosome initiation and elongation.	[50, 63, 64]
		Rubicon reduces IFN production and bind to NEMO to suppress ubiquitination and allows viral replication
HSV-1	Beclin 1	HSV inhibition of Beclin 1 to restrict autophagy	[50, 93]
Kaposi’s sarcoma herpes virus	Beclin 1	BCL2-like proteins cause inhibition of Beclin 1 and restricts autophagy	[50, 94]
HIV	Beclin 1	Accessory protein Nef binds/inhibits Beclin1 restricts autophagosome initiation and elongation	[50, 95]
Zika Virus	mTOR	NS4A and NS4B destabilize mTOR signaling	[96]
Sindbis Virus	ATG5, Beclin 1	Defects in ATG5 impairs CNS clearance of Sindbis virus capsid	[50, 97]
		Ectopic Beclin 1 expression in Sindbis virus-infected neurons suppresses viral replication in the brain and reduces mouse mortality.
Fungi	Autophagic machinery	Description	References
Aspergillus fumigatus	Rubicon, NOX2, LAP machinery	LAP-mediated degradation of and immune response to A. fumigatus	[14, 98]
Candida albicans	ATG5, Rubicon, NOX2	Rubicon binds to CARD9 and NEMO to suppress ubiquitination and allows for increased fungal burden	[62, 99]
Saccharomyces cerevisiae	ATG7	LAP required for fungal clearance	[27]
Cryptococcus neoformans	ATG5	ATG5 aids in delivering C. neoformans in LC3+ autolysosome	[99]
Parasites	Autophagic machinery	Description	References
Toxoplasma gondii	ATG14, ATG9, ATG5, ATG7, ATG12, ATG16L1	Autophagy is required for targeting and degradation of T. gondii	[28, 77]
Plasmodium vivax	Beclin 1, VPS34, ATG5	LAP required for parasite control	[100]

Pathogens (Bacteria, viruses, fungi, and parasites) with known links to components of the canonical and non-canonical autophagic machinery. Descriptions highlighted in green represent scenarios where pathogen clearance requires components of the autophagic machinery. Descriptions highlighted in red represent scenarios where autophagic components impede pathogen clearance.