title: Anti-infectious agents against MRSA.
abstract: Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA) has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652) targeting MRSA cell wall biosynthesis have been discovered using unique screening methods. These agents were found to inhibit important enzymes involved in cell wall biosynthesis such as undecaprenyl pyrophosphate (UPP) synthase, FemA, flippase, or UPP phosphatase. In this review, the discovery, the mechanism of action, and the future of these anti-infectious agents are described.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Koyama
authors.forename: Junji
authors.initials: J
authors.lastname: Inokoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002473:Cell Wall / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009183:Mycotoxins / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D010457:Peptidoglycan / Q000737:chemistry*; D013141:Spiro Compounds / Q000494:pharmacology; D013682:Teichoic Acids / Q000037:antagonists & inhibitors / Q000737:chemistry; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology; D037521:Virulence Factors; D024341:Xanthophylls / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C527434:BPH-652; D001426:Bacterial Proteins; D004224:Diterpenes; C096686:FemA protein, Bacteria; D009183:Mycotoxins; D009946:Organothiophosphorus Compounds; D010457:Peptidoglycan; D013141:Spiro Compounds; D013682:Teichoic Acids; D037521:Virulence Factors; D024341:Xanthophylls; D047090:beta-Lactams; C529277:cyslabdan; C573901:spirohexaline; D014640:Vancomycin; C031841:staphyloxanthin; D019883:Alkyl and Aryl Transferases; C023266:undecaprenyl pyrophosphate synthetase; D000111:Acetylcysteine