The pathogenesis of Legionella pneumophila, the etiological agent of the acute and sometimes fatal pneumonia called Legionnaires' disease, is presumably mediated by the ability of virulent L. pneumophila to survive and multiply within host macrophages. Avirulent L. pneumophila, which are easily isolated by passage on Mueller-Hinton agar medium are readily degraded within macrophages. Recent studies aimed at discerning differences between isogenic virulent and avirulent L. pneumophila indicated that virulent L. pneumophila enter host cells by a parasite directed mechanism involving surface protein structure of the bacterium. At least eight surface protein antigens are associated with virulent strains and, like the directed uptake phenotype, are lost when L. pneumophila is cultured in vitro. The role of the induced uptake phenotype and the virulence-associated surface proteins in pathogenesis is not known but it is thought that these virulence associated traits may influence the intracellular fate of L. pneumophila. The goal of this research proposal is to determine the contribution of directed uptake and the associated surface protein antigen to pathogenesis. This will be accomplished by 1) isolating the genes involved in the virulence associated phenotypes and characterizing the products of gene expression, 2) transferring the virulence associated genes to the isogenic avirulent counterpart in an attempt to restore virulence, and 3) mutagenizing the virulence associated gene in vitro and, by gene replacement, constructing strains from wild type parents that lack only a single functional gene. The mutants described will then be tested in appropriate in vitro and animal models to assess the role of the directed uptake phenotype and the associated expression of surface proteins to intracellular survival and pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI024684-02
Application #
3454057
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555