SPORE PEPTIDOGLYCAN DEGRADATION IN BACILLUS ANTHRACIS

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DESCRIPTION (provided by applicant): The infectious agent in anthrax is the dormant B. anthracis spore, and establishment of infection requires germination and outgrowth of the spore. Degradation of the spore cortex peptidoglycan wall during germination is necessary to allow rehydration and resumption of metabolism in the spore core. Cortex lytic enzymes are present in an inactive form in the spore and are activated only in the presence of specific germinant molecules. Goals of the proposed studies are identification of the important B. anthracis cortex lytic enzymes, characterization of their activities, and understanding of the mechanisms for their activation. Structures of the peptidoglycan found in B. anthracis dormant and germinating spores will be determined in order to identify cortex lytic activities operating during germination. Genes predicted to encode cortex lytic enzymes, based upon sequence similarities, will be disrupted and changes in germination lytic activities in the mutant strains will be characterized. Cortex lytic enzymes will be extracted and purified from germinating B. anthracis spores. The enzymatic activities and identities of these proteins will be determined. A greater understanding of the process of spore cortex lysis will suggest possible methods for combating anthrax infection on two fronts. Identification of drugs or treatments that block cortex lysis will allow treatment of individuals exposed to spores to prevent establishment of infection. Identification of chemicals or treatments that activate cortex lysis, resulting in germination and rendering the spores susceptible to standard bactericidal agents, will allow easier decontamination of spore-contaminated sites and prevention of human exposure.