Date of Award

Winter 1989

Project Type

Dissertation

Program or Major

Microbiology

Degree Name

Doctor of Philosophy

First Advisor

Frank Rodgers

Abstract

Legionella pneumophila is the causative agent of a severe, often fatal pneumonic illness known as Legionnaires' disease. The mechanisms by which L. pneumophila attaches to U937 (transformed human-like fibroblasts) were investigated. Experimental parameters for adherence assays were established prior to blocking studies designed to identify microbial adhesins and/or eukaryotic receptors that mediate bacterial attachment to target cells. Results from these studies indicated that a lectin-like component(s) associated with L. pneumophila may be responsible, at least in part, for microbial adherence to these eukaryotic host cells. Erythromycin is the drug of choice for the treatment of clinical legionellosis; however, difficulties with this antibiotic have been reported resulting in the need to seek alternative therapeutic regimens. In these studies, the effect of clinically relevant antibiotics that inhibited bacterial cell wall, protein and DNA synthesis of this pathogen was evaluated in vitro by growth and viability studies as well as morphologically by negative stain, scanning and thin-section electron microscopy. Of those tested, cefotaxime, an antibiotic of limited value in clinical trials, was most effective. The pathogenicity of L. pneumophila was assessed by LD$\sb{50}$ and bacterial growth estimations in the chick embryo animal system in ovo. In addition, histopathological and electron microscopic examination of the cellular and sub-cellular pathology induced in the organs of embryos previously infected with 100 times the yolk sac (YS)LD$\sb{50}$ of L. pneumophila was made as a prelude to chemotherapeutic treatment with a range of clinically putative antimicrobial agents. The promising new quinolone derivative, ciprofloxacin, was most effective in these trials. Results from these studies may be indicative of novel preventative and control measures for the therapy of human Legionnaires' disease.

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