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. 2012;4(1-2):21-32.

Potential Antibacterial Targets in Bacterial Central Metabolism

Nichole Louise Haag  1 , Kimberly Kay Velk, Chun Wu
Affiliations

Potential Antibacterial Targets in Bacterial Central Metabolism

Nichole Louise Haag et al. Int J Adv Life Sci. 2012.

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.

Keywords: Methicillin/multidrug-resistant Staphylococcus aureus; antibiotic resistance; central metabolism; drug targets; essential genes.

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Figures

Figure.1
Figure.1
Alignment of the amino acid sequences of MRSA FBPA (NCBI GENE ACCESSION#:49484349 and 15925115 respectively) with class II giardia FBPA (2ISV) and class I human FBPA (1QO5). Numbering of the amino acids is indicated on the left. Identical amino acid residues in the alignment are indicated in light-blue shading and similar amino acid residues are indicated in purple shading. Gaps introduced during the alignment process are indicated as dots.
Figure.2
Figure.2
Alignment of the amino acid sequences of MRSA acetate kinase with E. coli, Salmonella typhimurium ,Methanosarcina themophia ,Lactobacillus sanfranciscensis acetate kinases. Numbering of the amino acids is indicated on the left. Identical amino acid residues in the alignment are indicated in light-blue shading and similar amino acid residues are indicated in purple shading. Gaps introduced during the alignment process are indicated as dote
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