Metaeffector Exploits Host Proteasome to Temporally Regulate Cognate Effector
Pathogen-associated secretion systems translocate numerous effector proteins into eukaryotic host cells to coordinate cellular processes important for infection. Spatiotemporal regulation is therefore important for modulating distinct activities of effectors at different stages of infection. Here we provide the first evidence of “metaeffector,” a designation for an effector protein that regulates the function of another effector within the host cell. Legionella LubX protein functions as an E3 ubiquitin ligase that hijacks the host proteasome to specifically target the bacterial effector protein SidH for degradation. Delayed delivery of LubX to the host cytoplasm leads to the shutdown of SidH within the host cells at later stages of infection. This demonstrates a sophisticated level of coevolution between eukaryotic cells and L. pneumophila involving an effector that functions as a key regulator to temporally coordinate the function of a cognate effector protein.
Vyšlo v časopise:
Metaeffector Exploits Host Proteasome to Temporally Regulate Cognate Effector. PLoS Pathog 6(12): e32767. doi:10.1371/journal.ppat.1001216
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1001216
Souhrn
Pathogen-associated secretion systems translocate numerous effector proteins into eukaryotic host cells to coordinate cellular processes important for infection. Spatiotemporal regulation is therefore important for modulating distinct activities of effectors at different stages of infection. Here we provide the first evidence of “metaeffector,” a designation for an effector protein that regulates the function of another effector within the host cell. Legionella LubX protein functions as an E3 ubiquitin ligase that hijacks the host proteasome to specifically target the bacterial effector protein SidH for degradation. Delayed delivery of LubX to the host cytoplasm leads to the shutdown of SidH within the host cells at later stages of infection. This demonstrates a sophisticated level of coevolution between eukaryotic cells and L. pneumophila involving an effector that functions as a key regulator to temporally coordinate the function of a cognate effector protein.
Zdroje
1. IngmundsonA
DelpratoA
LambrightDG
RoyCR
2007 Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 450 365 369
2. MachnerMP
IsbergRR
2006 Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev Cell 11 47 56
3. MachnerMP
IsbergRR
2007 A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science 318 974 977
4. MurataT
DelpratoA
IngmundsonA
ToomreDK
LambrightDG
2006 The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat Cell Biol 8 971 977
5. FuY
GalanJE
1999 A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 401 293 297
6. HardtWD
ChenLM
SchuebelKE
BusteloXR
GalanJE
1998 S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93 815 826
7. KuboriT
GalanJE
2003 Temporal regulation of salmonella virulence effector function by proteasome-dependent protein degradation. Cell 115 333 342
8. BackertS
SelbachM
2005 Tyrosine-phosphorylated bacterial effector proteins: the enemies within. Trends Microbiol 13 476 484
9. PetterssonJ
NordfelthR
DubininaE
BergmanT
GustafssonM
1996 Modulation of virulence factor expression by pathogen target cell contact. Science 273 1231 1233
10. FieldsBS
1996 The molecular ecology of legionellae. Trends Microbiol 4 286 290
11. HorwitzMA
1983 The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome lysosome fusion in human monocytes. J Exp Med 158 2108 2126
12. SwansonMS
IsbergRR
1995 Association of Legionella pneumophila with the macrophage endoplasmic reticulum. Infect Immun 63 3609 3620
13. TilneyLG
HarbOS
ConnellyPS
RobinsonCG
RoyCR
2001 How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane. J Cell Sci 114 4637 4650
14. FieldsBS
BensonRF
BesserRE
2002 Legionella and Legionnaires' disease: 25 years of investigation. Clin Microbiol Rev 15 506 526
15. SegalG
PurcellM
ShumanHA
1998 Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. Proc Natl Acad Sci USA 95 1669 1674
16. VogelJP
AndrewsHL
WongSK
IsbergRR
1998 Conjugative transfer by the virulence system of Legionella pneumophila. Science 279 873 876
17. ShinS
RoyCR
2008 Host cell processes that influence the intracellular survival of Legionella pneumophila. Cell Microbiol 10 1209 1220
18. FrancoIS
ShumanHA
CharpentierX
2009 The perplexing functions and surprising origins of Legionella pneumophila type IV secretion effectors. Cell Microbiol 11 1435 1443
19. GoldsteinG
ScheidM
HammerlingU
SchlesingerDH
NiallHD
1975 Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proc Natl Acad Sci U S A 72 11 15
20. HershkoA
HellerH
EliasS
CiechanoverA
1983 Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem 258 8206 8214
21. VogesD
ZwicklP
BaumeisterW
1999 The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68 1015 1068
22. JacksonPK
EldridgeAG
FreedE
FurstenthalL
HsuJY
2000 The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol 10 429 439
23. PattersonC
2002 A new gun in town: the U box is a ubiquitin ligase domain. Sci STKE 2002 PE4
24. HicksSW
GalanJE
2009 Hijacking the host ubiquitin pathway: structural strategies of bacterial E3 ubiquitin ligases. Curr Opin Microbiol
25. QuezadaCM
HicksSW
GalanJE
StebbinsCE
2009 A family of Salmonella virulence factors functions as a distinct class of autoregulated E3 ubiquitin ligases. Proc Natl Acad Sci U S A 106 4864 4869
26. SingerAU
RohdeJR
LamR
SkarinaT
KaganO
2008 Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases. Nat Struct Mol Biol 15 1293 1301
27. ZhuY
LiH
HuL
WangJ
ZhouY
2008 Structure of a Shigella effector reveals a new class of ubiquitin ligases. Nat Struct Mol Biol 15 1302 1308
28. AngotA
VergunstA
GeninS
PeetersN
2007 Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems. PLoS Pathog 3 e3
29. RytkonenA
HoldenDW
2007 Bacterial interference of ubiquitination and deubiquitination. Cell Host & Microbe 1 13 22
30. KuboriT
HyakutakeA
NagaiH
2008 Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol Microbiol 67 1307 1319
31. Al-KhodorS
PriceCT
HabyarimanaF
KaliaA
Abu KwaikY
2008 A Dot/Icm-translocated ankyrin protein of Legionella pneumophila is required for intracellular proliferation within human macrophages and protozoa. Mol Microbiol 70 908 923
32. EnsmingerAW
IsbergRR
2010 E3 ubiquitin ligase activity and targeting of BAT3 by multiple Legionella pneumophila translocated substrates. Infect Immun 78 3905 3919
33. LommaM
Dervins-RavaultD
RolandoM
NoraT
NewtonHJ
2010 The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication. Cell Microbiol 12 1272 1291
34. PriceCT
Al-KhodorS
Al-QuadanT
Abu KwaikY
2010 Indispensable role for the eukaryotic-like ankyrin domains of the ankyrin B effector of Legionella pneumophila within macrophages and amoebae. Infect Immun 78 2079 2088
35. PriceCT
Al-QuadanT
SanticM
JonesSC
Abu KwaikY
2010 Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila. J Exp Med 207 1713 1726
36. ShohdyN
EfeJA
EmrSD
ShumanHA
ChenJ
2005 Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking. Proc Natl Acad Sci U S A 102 4866 4871
37. LuoZQ
IsbergRR
2004 Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc Natl Acad Sci U S A 101 841 846
38. NagaiH
CambronneED
KaganJC
AmorJC
KahnRA
2005 A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. Proc Natl Acad Sci U S A 102 826 831
39. SoryMP
CornelisGR
1994 Translocation of a hybrid YopE-adenylate cyclase from Yersinia enterocolitica into HeLa cells. Mol Microbiol 14 583 594
40. NagaiH
KaganJC
ZhuJ
KahnRA
RoyCR
2002 A Bacterial Guanine Nucleotide Exchange Factor Activates ARF on Legionella Phagosomes. Science 295 679 682
41. DerreI
IsbergRR
2005 LidA, a translocated substrate of the Legionella pneumophila type IV secretion system, interferes with the early secretory pathway. Infect Immun 73 4370 4380
42. ShinzawaN
NelsonB
AonumaH
OkadoK
FukumotoS
2009 p38 MAPK-Dependent Phagocytic Encapsulation Confers Infection Tolerance in Drosophila. Cell Host & Microbe 6 244 252
43. DorerMS
KirtonD
BaderJS
IsbergRR
2006 RNA interference analysis of Legionella in Drosophila cells: exploitation of early secretory apparatus dynamics. PLoS Pathog 2 e34
44. JanjusevicR
AbramovitchRB
MartinGB
StebbinsCE
2006 A bacterial inhibitor of host programmed cell death defenses is an E3 ubiquitin ligase. Science 311 222 226
45. BergerKH
IsbergRR
1993 Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol Microbiol 7 7 19
46. FeeleyJC
GibsonRJ
GormanGW
LangfordNC
RasheedJK
1979 Charcoal-yeast extract agar: primary isolation medium for Legionella pneumophila. J Clin Microbiol 10 437 441
47. ZuckmanDM
HungJB
RoyCR
1999 Pore-forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth. Mol Microbiol 32 990 1001
48. KaganJC
RoyCR
2002 Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat Cell Biol 4 945 954
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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