Abstract

Legionella pneumophila is a valuable model organism for identifying bacterial determinants that modulate vesicular transport. Central to the process of L. pneumophila manipulation of host membrane trafficking is a type IV-related protein secretion system called Dot/lcm that is required for the establishment of a vacuole that supports bacterial replication in eukaryotic cells. The goal of this grant is to understand how the Dot/lcm system governs biogenesis of the specialized vacuole in which L. pneumophila replication occurs. We have identified and determined the biological activities for several L. pneumophila effector proteins translocated into host cells by the Dot/lcm system. Our goal over the next granting period will be to elucidate the molecular mechanisms that underlie the functioning of these Dot/lcm effectors to understand how they manipulate host proteins important for replication of L. pneumophila inside of eukaryotic cells. This work will provide a more detailed understanding of how Dot/lcm effector proteins modulate host cell interactions to facilitate the intracellular replication and pathogenesis of L. pneumophila. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041699-13
Application #
7437337
Study Section
Special Emphasis Panel (ZRG1-IDM-A (02))
Program Officer
Korpela, Jukka K
Project Start
1997-07-01
Project End
2012-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
13
Fiscal Year
2008
Total Cost
$398,184
Indirect Cost

  Institution

Name
Yale University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Arasaki, Kohei; Kimura, Hana; Tagaya, Mitsuo et al. (2018) Legionella remodels the plasma membrane-derived vacuole by utilizing exocyst components as tethers. J Cell Biol 217:3863-3872
Shames, Stephanie R; Liu, Luying; Havey, James C et al. (2017) Multiple Legionella pneumophila effector virulence phenotypes revealed through high-throughput analysis of targeted mutant libraries. Proc Natl Acad Sci U S A 114:E10446-E10454
Tørring, Thomas; Shames, Stephanie R; Cho, Wooyoung et al. (2017) Acyl Histidines: New N-Acyl Amides from Legionella pneumophila. Chembiochem 18:638-646
Kohler, Lara J; Roy, Craig R (2017) Autophagic targeting and avoidance in intracellular bacterial infections. Curr Opin Microbiol 35:36-41
Marion, Chad R; Wang, Jianmiao; Sharma, Lokesh et al. (2016) Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1? and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia. Infect Immun 84:2094-2104
Horenkamp, Florian A; Kauffman, Karlina J; Kohler, Lara J et al. (2015) The Legionella Anti-autophagy Effector RavZ Targets the Autophagosome via PI3P- and Curvature-Sensing Motifs. Dev Cell 34:569-76
Hubber, Andree; Arasaki, Kohei; Nakatsu, Fubito et al. (2014) The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins. PLoS Pathog 10:e1004222
Horenkamp, Florian A; Mukherjee, Shaeri; Alix, Eric et al. (2014) Legionella pneumophila subversion of host vesicular transport by SidC effector proteins. Traffic 15:488-99
Del Campo, Claudia M; Mishra, Ashwini K; Wang, Yu-Hsiu et al. (2014) Structural basis for PI(4)P-specific membrane recruitment of the Legionella pneumophila effector DrrA/SidM. Structure 22:397-408
Choy, Augustine; Roy, Craig R (2013) Autophagy and bacterial infection: an evolving arms race. Trends Microbiol 21:451-6

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