Metabolite Concentration as a Criterion for Antibacterial Discovery
The discovery and use of antibacterials represents a primary success of modern pharmaceutical industry.
However, the pace of antibacterial discovery was heavily hindered by a series of technical difficulties and the unfavorable
economics in recent years. The past decade has witnessed rapid progresses in omics and systems biology, which provided
an unprecedented opportunity to accelerate the discovery of antibacterials. In this article, we first summarize the
successful use of metabolic network analysis in antibacterial discovery. Then, we reveal that metabolite concentration
serves as a useful criterion for selecting antimicrobial targets. The essential enzymes with low substrate concentrations (<
0.5 mM) are more druggable antibacterial targets. Besides, we find that the solubility of clinically used competitive
antibacterials is at least 100 times higher than the concentrations of the competed substrates. By the new-proposed
criterion, we not only identify some promising antibacterial targets but also explain some perplexing experimental
observations as well.
Keywords: Antibacterial discovery, antibacterial target, bioinformatics, flux balance analysis (FBA), metabolic network,
metabolite concentration, metabolomics, systems biology.
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