title: Targeting bacterial central metabolism for drug development.
abstract: Current antibiotics, derived mainly from natural sources, inhibit a narrow spectrum of cellular processes, namely DNA replication, protein synthesis, and cell wall biosynthesis. With the worldwide explosion of drug resistance, there is renewed interest in the investigation of alternate essential cellular processes, including bacterial central metabolic pathways, as a drug target space for the next generation of antibiotics. However, the validation of targets in central metabolism is more complex, as essentiality of such targets can be conditional and/or contextual. Bearing in mind our enhanced understanding of prokaryotic central metabolism, a key question arises: can central metabolism be bacteria's Achilles' heel and a therapeutic target for the development of new classes of antibiotics? In this review, we draw lessons from oncology and attempt to address some of the open questions related to feasibility of targeting bacterial central metabolism as a strategy for developing new antibacterial drugs.
authors.affiliation: Laboratory of Microbiology and Microsystems, Global Health Institute, Swiss Federal Institute of Technology (EPFL), EPFL/SV/GHI/UPKIN, Station 19, 1015 Lausanne, Switzerland. Electronic address: paul.murima@epfl.ch.
authors.forename: Paul
authors.initials: P
authors.lastname: Murima
authors.affiliation: Laboratory of Microbiology and Microsystems, Global Health Institute, Swiss Federal Institute of Technology (EPFL), EPFL/SV/GHI/UPKIN, Station 19, 1015 Lausanne, Switzerland.
authors.forename: John D
authors.initials: JD
authors.lastname: McKinney
authors.affiliation: Antibacterial Drug Discovery Unit, Institute Pasteur Korea, Sampyeong-dong 696, South Korea; Lee Kong Chian School of Medicine and School of Biological Sciences, Nanyang Technological University, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore. Electronic address: kevin.pethe@ntu.edu.sg.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pethe
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004734:Energy Metabolism / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009243:NAD / Q000096:biosynthesis; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D014815:Vitamins / Q000096:biosynthesis
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D014815:Vitamins; D009243:NAD; D010447:Peptide Hydrolases