This research proposal is focused on the significance of multiple gene copies for protein P1 with regards to the observed biological role of P1 as an integral adhesin necessary for cytadherence of Mycoplasma pneumoniae to human respiratory epithelium. Emphasis is place on defining at the molecular level the epitopes within P1 necessary for cytadherence and detecting antigenic or biological alterations in these epitopes in wild-type, mutant and clinical isolate populations. The definition of functional epitopes within P1 and the identification of unique-sequences form P1-related gene fragments will be used to explore the factors which affects the expression and biological role of adhesin P1 in virulence. Technologies to be used range from cloning and sequencing of P1 and P1-related gene sequences to analysis of mRNA transcripts and development of expression systems for M. pneumoniae proteins. In addition, synthetic peptides will be examined from vaccine and serodiagnostic value and will assist in characterization of host receptors. We expect that other activities of P1 will be uncovered in addition to those related to cytadherence. It is expected that information obtained from this study will result in a significantly better molecular understanding of the virulence process of Mycoplasma pneumoniae. This understanding will ultimately lead to interventions for the prevention of pneumonia cause by M. pneumoniae and related infections. More generally, these studies will further the understanding of the role of gene conversion in the alteration of protein domains with biofunctional significance.
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