Identification of New Drug Targets in Multi-Drug Resistant Bacterial Infections.

摘要

A. baumannii is a gram-negative bacillus (GNB) known to cause health-care associated infections. Recently, community-acquired infections, infections in wounded U.S. service members, and infections in residents of long-term care facilities have been reported. Safe reliable agents with predictable activity against A. baumannii are presently non-existent. Improved outcomes will require the development of new therapeutics. We aim to accomplish this is by identifying and examining two biosynthetic pathways as potential antimicrobial targets in A. baumannii. Our investigation of protein targets in A. baumannii includes two goals. First, we will validate and evaluate the druggability of enzymes from the chorismate pathway of A. baumannii. Second, we will examine and characterize a novel biosynthetic cluster that encodes non-ribosomal peptide synthetase (NRPS) enzymes that have been demonstrated to be involved in bacterial motility and to be upregulated in response to quorum signaling molecules.