Mycobacterium tuberculosis, MTb, accounts for the largest infectious cause of human mortality worldwide, a title that is reinforced by its synergy and co-morbidity with AIDS and the emergence of multi-drug resistant MTb strains. The complete MTb genome contains at least 10 predicted loci dedicated to the synthesis of polyketides and related compounds. Polyketide-like compounds are well known and appreciated for their pharmacological utilities, including antitumor, antibiotic, immunosuppressive and anti-hypercholesterolimic effects to name but a few. The current proposal seeks to evaluate the relevance of polyketides in MTb pathogenesis. Specifically, we aim to characterize the structure of MTb polyketides and to analyze their timctional roles in mediating microbial virulence and persistence via functions they confer on the bacilli or by alterations m normal processes of host immunity. Our ultimate aim is to clarify roles of microbial metabolites in pathogenesis and virulence with a view to discover novel targets for therapeutic intervention in infectious disease processes.
| Chavadi, Sivagami Sundaram; Onwueme, Kenolisa C; Edupuganti, Uthamaphani R et al. (2012) The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids. Microbiology 158:1379-87 |
| Onwueme, Kenolisa C; Vos, Cheryl J; Zurita, Juan et al. (2005) Identification of phthiodiolone ketoreductase, an enzyme required for production of mycobacterial diacyl phthiocerol virulence factors. J Bacteriol 187:4760-6 |
| Buglino, John; Onwueme, Kenolisa C; Ferreras, Julian A et al. (2004) Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis. J Biol Chem 279:30634-42 |
