Date of Award
Program or Major
Doctor of Philosophy
Frank G Rodgers
Legionella pneumophila is a facultative intracellular bacterial pathogen which initiates infection of the human host by adhering to macrophages in the alveoli of the lung following which internalization and intracellular multiplication occurs. In this study a novel mechanism of opsonin-independent attachment for this organism to host cells was identified. L. pneumophila serogroup 1, strain Nottingham N7, and U-937 cells as well as primary guinea pig alveolar macrophages were used to study this adherence phenomenon.
A variety of assay methods were used to evaluate the nature of this binding event: transmission electron microscopy and scanning electron microscopy were used to visualize the uptake and replicative processes while organism enumeration as a measure of adherence was accomplished using viable bacterial cell colony counts and indirect immunofluorescence studies. It was shown that L. pneumophila adhered to U-937 cells in the absence of complement and a complete infectious cycle for the organism was found. These data confirmed previously identified stages of phagocytic host cell interaction including uptake, intracellular replication and release of progeny bacteria.
The chemical nature of the L. pneumophila bacterial "adhesin" and the host cell "receptor" in binding studies were investigated. The results from both competitive binding and surface treatment studies suggested the nature of the putative adhesins and receptor moieties associated with successful attachment of L. pneumophila to these host cells. Glycolipids on host cell surfaces and proteins or glycoproteins on Legionella membranes function to facilitate binding of bacteria prior to engulfment.
Monoclonal antibodies specific for complement receptors CR1, CR3 and CR4 were used in blocking studies and these indicated that these molecules were not involved in the recognition of legionellae. These results indicate the importance of opsonin-independent binding mechanisms for L. pneumophila to host cells and shed new light on our understanding of cellular infection by L. pneumophila.
Gibson, Frank Clinton, "The role of opsonin-independent bacterial adherence in the pathogenesis of Legionnaires' disease" (1994). Doctoral Dissertations. 1781.