Mycoplasma Pneumoniae Infections - Role of Nucleotide Metabolism in the Mechanism of Pathogenesis

174 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1982.The method by which Mycoplasma pneumoniae induces a cytopathic effect (CPE) in host cells is not clearly defined. This study was designed to delineate some of the factors involved in the mechanism of pathogenesis of M. pneumoniae infection. Two major areas affecting the host-parasite interaction were studied. These included the relationship of the host cell metabolism with the ability of the mycoplasmas to induce a CPE in MRC-5 human lung fibroblasts, and alterations in the metabolism of the host cells due to mycoplasma infection.In order to accelerate or depress cellular metabolic activities, the MRC-5 cells were grown in various serum concentrations, at different densities, or for various lengths of time. DNA, RNA, and protein syntheses in the fibroblasts were measured for each treatment. The cells were also infected with M. pneumoniae. The CPE caused by the mycoplasmas correlated closely with nucleic acid metabolism of the host cells. A pronounced CPE developed in cells infected with M. pneumoniae while the cells were actively synthesizing DNA and RNA. Conversely, little or no CPE developed in cells which were infected while they were quiescent.M. pneumoniae infection of the MRC-5 cells caused alterations in several of the metabolic pathways of the MRC-5 cells. These included an inhibition of de novo purine synthesis, stimulation of DNA synthesis, and stimulation of purine salvage. Lesch-Nyhan fibroblasts, deficient in purine salvage enzymes, rely heavily on de novo purine synthesis. They were significantly more susceptible to mycoplasma infection than were the normal MRC-5 cells. This indicated that the inhibition of de novo purine synthesis is an important step in the development of a cytopathic effect in cells infected with M. pneumoniae. In addition, the nucleotide concentrations of the mycoplasma infected cells were altered. The nucleoside triphosphate content was lower in the infected MRC-5 cells, while the nucleoside mono- and diphosphate contents were lower in the normal cells.These data indicate the importance of nucleotide metabolism (i.e. DNA synthesis, RNA synthesis, purine salvage, de novo purine synthesis and regulation of nucleotide content) in M. pneumoniae infections. This may explain, in part, the biochemical basis for virulence in this pathogen.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD