Bacterial interaction with host autophagy

Figures & data

Figure 1. Anti-bacterial autophagy. (a) Domains of autophagy receptors. PB1, Phox and Bem1p domain; ZZ, ZZ-type zinc finger domain; TB, TRAF6-binding region; LIR, LC3-interacting region; KIR, Keap1-interacting region, UBA, ubiquitin-associated; FW, four W domain; SKICH, skeletal muscle and kidney-enriched inositol phosphatase carboxyl homology; CLIR, non-canonical LIR; CC, coiled-coil; GIR, galectin-8 interacting region; UBZ, ubiquitin-binding zinc finger; UBAN, ubiquitin-binding in ABIN and NEMO; ZnF, Zn-finger. (b) Ubiquitin-dependent and ubiquitin-independent pathways involved in autophagic elimination of intracellular Mtb and Salmonella. NOX, NADPH oxidase; ROS, reactive oxygen species; OTULIN, ovarian tumor (OTU) domain-containing deubiquitinase (also known as Gumby and Fam105b), IKK, IκB kinase, IL, interleukin.

Table 1. Mechanisms involved in the interaction of intracellular bacteria with host autophagy.

Bacterium	Effectors	Host targets	Function	Refs.
Shigella flexneri	IcsB	ATG5 Small GTPases SNARE CHMP5 (ESCRT-III complex)	Preventing ATG5 recognition of IcsA; counteracting recruitment of Tecpr1, spetins, ubiquitin, p62 and NDP52; interfering with membrane trafficking	[43,79–82]
	IcsB	Toca-1	Preventing recognition by NDP52	[95]
	VirA	Rab1A	Inactivating Rab1 as a GAP, inhibiting autophagy induction	[59]
	OspB	IQGAP1	Activating mTORC1	[96]
Legionella pneumophila	RavZ	Ubiquitin?	Preventing ubiquitin recruitment	[72]
	RavZ	LC3-PE	Deconjugating LC3-PE, inhibiting autophagosome formation	[67,69,70]
	LpSpl	Sphingolipids	Interfering with host sphingosine biosynthesis	[74]
	SidE	Rag GTPases	Inhibiting mTORC1 via ubiquitination of Rag	[97]
	Lgt	eEF1A, mTORC1	Inhibiting protein synthesis and activating mTORC1 via liberation of amino acids	[97]
	Lpg1137	Stx17	Depleting Stx17, inhibiting autophagosome biogenesis	[73]
Mycobacterium tuberculosis	Eis	MKP-7, JNK	Acetylating and activating MKP-7 that inactivates JNK, inhibiting autophagy induction	[61]
	SapM, PknG	Rab5 and Rab7	Inhibiting Rab5-Rab7 exchange and autophagosome maturation	[75]
	CpsA	NADPH oxidase	Inhibiting recruitment of Mtb to LC3-associated phagosomes	[98]
	HBHA	LC3	Inhibiting LC3 expression and the maturation of autophagosomes	[99]
M. tuberculosis H37Rv	PhoP and ESAT-6	Rab7	Inhibiting autophagosome maturation	[76]
Mycobacterium marinum	ESX-1	TORC1	Blocking the autophagic flux	[100]
Listeria mono-cytogenes	ActA	Arp2/3	Catalysing actin polymerization on the bacterial surface to disguise from autophagic recognition	[83,84]
	InlK	MVP	Preventing cytosolic bacteria from autophagic recognition	[85]
	PlcA, PlcB	PI3P	Reducing PI3P levels to inhibit pre-autophagosomal structures	[65]
Salmonella Typhimurium	SseF and SseG	Rab1A-TRAPPIII	Disrupting Rab1A-TRAPPIII interaction and therefore Rab1A activation, inhibiting autophagy induction	[58]
	SPI2	Sirt1, LKB1, AMPK	Inducing lysosomal degradation of Sirt1, LKB1 and AMPK, activating mTOR, inhibiting autophagy initiation	[57]
Staphylococcus aureus	Hla	Unknown	Activating autophagy pathway independent of PI3KC3 and Beclin1	[88]
	IsaB	Unknown	Inhibiting autophagsome maturation	[89]
	Unknown	MAPK14, ATG5	Inibiting autophgosome maturation	[90]
Group A Streptococcus (GAS)	SpeB	p62, NDP52, NBR1	Degrading autophagy receptors to prevent recognition by host autophagy	[86]
	Streptolysin O (SLO), NADase	Unkown	Preventing maturation of the GAS-containing autophagosome-like vacuoles	[101]
Francisella tularensis	Type VI secretion system	Beclin1	Hijacking autophagy machinery to derive nutrients for replication in an ATG5-independent autophagy pathway	[102]
Escherichia coli O157:H7	Tir	PKA	Activating protein kinase A	[103]
Burkholderia pseudomallei	BopA	Unknown	23% identity with IcsB of Shigella	[104]

Figure 2. Manipulation of autophagy pathways by bacterial factors. Intracellular bacteria have evolved mechanisms to escape host autophagy in order to survive and replicate in host cells. Eis (Mtb), VirA and OspB (Shigella), EspG (EPEC), SseF/G (Salmonella), and Lpg1137 (Legionella) inhibit autophagy induction. RavZ, Lpg1137, and LpSpl (Legionella), and PlcA/B (Listeria) inhibit autophagosomes formation, SpeB (GAS), ActA and InlK (Listeria), and IcsB (Shigella) prevent recognition by host autophagy. SapM, PknG and HBHA (Mtb), ESAT-6 and PhoP (Mtb H37Rv), IsaB (S. aureus), SLO and NADase (GAS) inhibit autophagosome-lysosome fusion.

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