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15 Cards in this Set
- Front
- Back
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Legionella pneumophila |
-Gram -, rod, motile -intracellular -environmental organism |
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Legionnaires' disease(legionellosis) |
-sever penumonia, transmission through droplets or ventilation systems -elderly, immunosuppressed |
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Primary site in human |
alveolar macrophages |
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Life cycle of legionella in protozoa |
cycle in protozoa increases virulence of legionella. 1. adhesion/invasion 2. replication in vacuole 3. lyse vacuole and released in environment |
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Life cycle in macrophage |
1. phagocytosis, enters the cell 2. abundance of AA triggers bacterial replciation 3. nutritional starvation triggers exit and transmission to new cell by stringent response(ppGpp) |
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Formation of LCV(legionella containing vacuole) |
1. Mitochondria recruited near LCV 2. Vesicles derived from ER surround LCV 3. LCV becomes studded with ribosomes just like ER 4. Bacteria replicate within LCV 5. lyse the cell |
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The Dot/Icm type IV secretion system |
defective organelle traffickin, intracellular multiplication -Type 4 SS -250 effector proteins translocated -Dot/Icm mutant is avirulent -much functional redundancy |
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Dot/Icm effector targets |
1. Host GTPase -to highjack ER-golgi transport system 2. membrane phosphoinositides 3. host protein synthesis/ stress response 4. apoptosis 5. host ubiquitination |
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Target Rab GTPase |
Arf1 and Rab1: GTPases associated with vesicular traffic from ER to golgi -Legionelle effectors can complete the whole cycle of GTPase with its effectors. -effector RalF recruit Arf1 on bacterial vacuole and acts as GEF. - SidM/DrrA acts as GEF for Rab1 and AMPylate Rab1 making it CA. -SidD reverses AMPylation - LepB acts as Rab1 GAP - AnkX and Lem3 PC of Rab1. |
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Manipulation of phosphoinositide lipids |
PI: negatively charged glycerolipids, phosphorylated at different positions -specific phosphoinositides serve as anchors for various proteins on intracellular membranes -LCV is rich in PI 4-phosphate (usually on trans-golgi) - many T4SS effectors bind to LCV through interaction with PI 4-P -SidF (PI phosphatase) dephosphorylates 3-P |
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Host cell death pathways |
SidF binds to BNIP3(pro-apoptotic porteins) and Bcl-rambo, preventing mitochondria-mediated apoptosis. SdhA maintains integrity of LCV(prevent leaking PAMPs in cytoplasm) SdhA mutant causes rapid host cell death LegK1 activates NF-kB(anti-apoptotic), ser/thr kinase that phosphorylate/inactivates IkB and p100(inh of NfKB) LnaB activates NF-kB also. |
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Manipulation of ubiquitination machinery |
AnkB anchored to LCV by host-mediated farnesylation. Recruit Lys-48 polyubiquitinated proteins to LCV to generate AA for bacterial replication.
LubX targets SidH for ubiquitination and degradation |
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Manipulation of gene expression |
RomA: methyltransferase H3K14, target to nucleus by NLS. -resulting in repression -4870 genes associated with H3k9. |
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Manipulation of protein translation |
- 5 T4SS effectors inhibits translation elongation - Inhibit eEF1A. |
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Innate immune response to legionella |
Lipid A recognized by TLR 2 not TLR4 -TLR5 polymorphism with stop codon in ligand binding domain of TLR5 high susceptibility to pneumonia (by legionella) -because higher production of IL-8 (recruit neutrophils) |
