title: Combating multidrug-resistant bacteria: current strategies for the discovery of novel antibacterials.
abstract: The introduction of effective antibacterial therapies for infectious diseases in the mid-20th century completely revolutionized clinical practices and helped to facilitate the development of modern medicine. Many potentially life-threatening conditions became easily curable, greatly reducing the incidence of death or disability resulting from bacterial infections. This overwhelming historical success makes it very difficult to imagine life without effective antibacterials; however, the inexorable rise of antibiotic resistance has made this a very real and disturbing possibility for some infections. The ruthless selection for resistant bacteria, coupled with insufficient investment in antibacterial research, has led to a steady decline in the efficacy of existing therapies and a paucity of novel structural classes with which to replace them, or complement their use. This situation has resulted in a very pressing need for the discovery of novel antibiotics and treatment strategies, the development of which is likely to be a key challenge to 21st century medicinal chemistry.
authors.affiliation: Departments of Chemistry and Biochemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (United Kingdom) http://www-spring.ch.cam.ac.uk.
authors.forename: Kieron M G
authors.initials: KM
authors.lastname: O'Connell
authors.forename: James T
authors.initials: JT
authors.lastname: Hodgkinson
authors.forename: Hannah F
authors.initials: HF
authors.lastname: Sore
authors.forename: Martin
authors.initials: M
authors.lastname: Welch
authors.forename: George P C
authors.initials: GP
authors.lastname: Salmond
authors.forename: David R
authors.initials: DR
authors.lastname: Spring
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D001430:Bacteriocins / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D054892:Metagenome; D008969:Molecular Sequence Data; D053038:Quorum Sensing / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D001688:Biological Products
keywords: antibiotics; antivirulence; medicinal chemistry; natural products; resistance