title: Metabolite concentration as a criterion for antibacterial discovery.
abstract: 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.
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, Center for Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhu
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D001424:Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D049490:Systems Biology / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents