Bordetella pertussis, the causative agent of whooping cough, secrets multiple toxins which are presumed to be the cause of the systemic symptoms of the disease. Investigations on B. pertussis have shown that the bacterium produces an adenylate cyclase toxin which is activated by eukaryotic calmodulin. This adenylate cyclase toxin is one of the major virulence factors with B. pertussis. It is believed that the pathogenic mechanism involves the activation of the bacterial adenylate cyclase toxin by the host calmodulin causing over-production of cyclic-AMP in the host leading to alterations in cellular metabolism. Recently, biochemical experimentation has presented evidence of the existence of a calmodulin-like protein within B. pertussis and other bacteria. The purpose of this research is to elucidate the molecular details involved in the pathogenesis of B. pertussis infection. The proposed research will study the calmodulin-like protein present in B. pertussis by a) analyzing the chemical, physical and immunological properties of this protein, b) preparing oligonucleotide probes using the highly conserved region from residues 8-23 (which is identical in all calmodulins) to clone the gene, c) sequencing the cloned calmodulin gene and, d) evaluating the effects of this calmodulin on B. pertussis adenylate cyclase toxin. The long term goal of the research is to develop a more effective vaccine and to uncover novel developments towards the understanding of mechanisms of disease.
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