In immunocompromised and other severely ill patients, Pseudomonas aeruginosa (PA) causes an acute pneumonitis, which has an extremely high fatality rate. Improved methods for prevention and therapy are urgently needed. An in vitro model of PA infection using polarized Madin-Darby canine kidney (MDCK) cells or cultured lung epithelial cells mimics many important features of in vivo pneumonia. Live Pseudomonas organisms added to the apical surface of these cultures attach to and kill the cells. These foci of infection spread centripetally. The current proposal will study the host cell factors that determine susceptibility to Pseudomonas pneumonia using these in vitro model systems. There are four aims in this study: to investigate how modification of cell polarity affects virulence; to identify the receptors for PA and how their regulation affects bacterial interaction; to determine the pathway for internalization of PA organisms; and to examine the role of the actin cytoskeleton in interaction of PA with cells.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055980-07
Application #
6537251
Study Section
Lung Biology and Pathology Study Section (LBPA)
Program Officer
Colombini-Hatch, Sandra
Project Start
1995-09-30
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
7
Fiscal Year
2002
Total Cost
$239,574
Indirect Cost
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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