Identified virulence factors of Legionella: Secretion system
(Type II secretion system)
Related genes: lspD;
Keywords: Secretion system; Type II secretion system; Characteristics: This secretion system is encoded on 5 regions scattered over the chromosome in contrast to most other bacteria where the type II genes are clustered in one or two regions.
Functions: Critical for intracellular growth and virulence.
Transport two phosphatases, an RNase, a zinc metalloprotease (Msp), mono-, di- and triacylglycerol lipases, phospholipase A, a lysophospholipase A and a p-nitrophenyl phosphorylcholine hydrolase.
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Hales LM, Shuman HA, 1999. Legionella pneumophila contains a type II general secretion pathway required for growth in amoebae as well as for secretion of the Msp protease. Infect. Immun. 67(7):3662-3666.
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(defect in organella trafficking/intracellular multiplication)
Functions: Allows survival and growth in macrophages, prevent phagosome acidification and lysosome fusion, essential for induction of apoptosis in human macrophages.
Mechanism: Assemble and activate a type IV secretion system in the bacterial membrane that exports plasmid and virulence factors to inhibit the phago-lysosome fusion and reprogram the Legionella-bearing vacuole.
IcmS was shown to bind members of the SidE family (SidE, SdeA, SdeB, SdeC) and to be required for the export of SdeA.
IcmW interacted with and was required for the translocation of additional Dot/Icm substrates, including SidG, SidH, WipA and WipB.
LvgA directly interacts with IcmS.
Dot/Icm secretion substrates have been identified: DotA, a protein that was originally reported to assemble as a polytopic protein in the inner membrane of L. pneumophila cells. It may form a pore in the eukaryotic membrane for the passage of other effectors LidA (low viability in the presence of dot), a protein translocated to the phagosome membrane. It regulates Dot/Icm assembly and is thought to be one of the first translocated substrates. It is postulated to function in vesicle recruitment during the biogenesis of the replication vacuole RalF, an exchange factor for the ADP ribosylation factor protein (ARF) family of GTPases. It is required for the localization of ARF on phagosomes containing L. pneumophila. ARF is important for biogenesis of the replicative organelle DrrA (defect in Rab1 recruitment A, also known as SidM), is a multifunction enzyme with both GDF (GDI-displacement factor, GDI: guanine nucleotide dissociation inhibitor) and GEF (guanine nucleotide exchange factor) activities. DrrA has the intrinsic ability to bind to the cytosolic surface of the plasma membrane. Because the L. pneumophila-containing vacuole (LCV is) initially a plasma-membrane-derived organelle, translocated DrrA protein associates with the immature LCV formed on bacterial internalization. The GDF activity of DrrA promotes the sampling of cytosolic Rab proteins associated with Rab GDI. When Rab1-Rab-GDI complexes are sampled, the removal of Rab GDI permits the GEF domain in DrrA to activate Rab1, leading to the stable association of Rab1 with the LCV membrane. Active Rab1 facilitates organization of the LCV membrane to promote the delivery and fusion of ER-derived vesicles. DrrA cycles off because the composition of the vacuole membrane changes. LepB is a Rab1-specific GAP (GTPase-activating proteins). The LepB protein accumulates on the LCV membrane and the GAP activity facilitates the removal of Rab1 by stimulating GTP hydrolysis. The removal of Rab1 coincides with fusion of the LCV with the host ER and replication of L. pneumophila in a vacuole containing ER proteins. Other candidate effector proteins including SidA-G (substrate of Dot/Icm transporter), Vips (VPS(vacuole protein sorting) inhibitor proteins, VipA, VipD, VipE, VipF), SdeA-D, YlfAB (yeast lethal factor A and B), their real function are unknown.
Once the vacuole provides conditions for the bacteria to grow, functional genes of the dot/icm family become dispensable.
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