SCELSE Seminar Series: Targeting bacterial bioenergetics & central metabolism for drug development

Abstract:
The rapid emergence and spread of multi-drug resistant bacteria is a serious concern worldwide that advocates for the development of new classes of antibacterials with a novel mode of action. Current antibiotics derive mainly from natural sources and inhibit a narrow spectrum of cellular processes such as DNA replication, protein synthesis and cell wall biosynthesis. With the spread of drug resistance, there is a renewed interest in the investigation of alternate essential cellular processes, including central metabolic and bioenergetics pathways, as a drug target space for the next generation of antibiotics. However, the validation of those targets is more complex, as essentiality of such targets can be conditional. Interest in targeting central metabolism has also been muted because of a concern about selectivity with human orthologs. Nonetheless, selective inhibition can be achieved for enzymes that are conserved between bacteria and humans. I will present the relevance of targeting bioenergetics for the development of a rational drug combination for tuberculosis and other mycobacterial diseases, and metabolic vulnerabilities in gram-positive and gram-negative bacteria that could be exploited for drug development.

Speaker:
KEVIN PETHE
Associate Professor, Infectious Disease and Assistant Dean (Research), Lee Kong Chian School of Medicine;
Provost’s Chair in Infectious Disease; Associate Professor, Lee Kong Chian School of Medicine;
Associate Professor, School of Biological Sciences;
Principal Investigator, Singapore Centre for Environmental Life Sciences Engineering (SCELSE)