Potential Antibacterial Targets in Bacterial Central Metabolism.

Abstract

The emerging antibiotic resistant bacteria and their abilities for rapid evolution have pushed the need to explore alternative antibiotics less prone to drug resistance. In this study, we employed methicillin/multidrug-resistant Staphylococcus aureus (MRSA) as a model bacterial system to initiate novel antibiotic development. An in silico identification of drug targets in MRSA 252 strain and MRSA Mu50 strain respectively was described. The identified potential targets were classified according to their known or putative functions. We discovered that a class of essential non-human homologous, central metabolic enzymes falls into the scope of potential drug targets for two reasons: 1) the identified targets either do not have human counterparts or use alternative catalytic mechanisms. Based on major differences in active site structure and catalytic mechanism, an inhibitor of such a bacterial enzyme can be designed which will not inhibit its human cousin. 2) attacking bacterial energy-making machinery bypasses the usual drug resistance sites, paving the road to multi-faceted approaches to combat antibiotic resistance.