MYCOBACTERIUM AVIUM DNA B AND NOVEL DRUG TARGET

University Of Texas Hlth Ctr At Tyler, Tyler TX

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Abstract

DESCRIPTION: (Adapted from Applicant's Abstract) MACs are the most common cause of mycobacterial lung disease other than tuberculosis and are the leading cause of morbidity and mortality in HIV-infected AIDS patients. At present the antibiotics available for treating M.avium infections are inadequate. DNA replication leading to multiplication of a pathogen is the firat committed step in the onset of infection. Replication is believed to be regulated at the level of initiation. The present proposal focuses on the DnaB protein, whose analogs in other bacteria play a crucial role in replication initiation and the DnaB protein is essential for cellular growth. The interactions of the DnaB protein with the complexes of the origin of replication and DnaA, the putative initiator protein believed to mark the future forks for bidirtectional replication. The DnaB protein of M.avium, unlike many other bacterial DnaB, contains Intein in its sequence. Experiments proposed here will examine the roles of DnaB and Intein proteins, nature and functional consequences of Intein splicing in M.avium DNA replication and metabolism. The long term goal is to be able to develop drugs that will block the initiation process and thereby prevent growth and development of M.avium infections.