title: Development of antibiotic activity profile screening for the classification and discovery of natural product antibiotics.
abstract: Despite recognition of the looming antibiotic crisis by healthcare professionals, the number of new antibiotics reaching the clinic continues to decline sharply. This study aimed to establish an antibiotic profiling strategy using a panel of clinically relevant bacterial strains to create unique biological fingerprints for all major classes of antibiotics. Antibiotic mode of action profile (BioMAP) screening has been shown to effectively cluster antibiotics by structural class based on these fingerprints. Using this approach, we have accurately predicted the presence of known antibiotics in natural product extracts and have discovered a naphthoquinone-based antibiotic from our marine natural product library that possesses a unique carbon skeleton. We have demonstrated that bioactivity fingerprinting is a successful strategy for profiling antibiotic lead compounds and that BioMAP can be applied to the discovery of new natural product antibiotics leads.
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064, USA.
authors.forename: Weng Ruh
authors.initials: WR
authors.lastname: Wong
authors.forename: Allen G
authors.initials: AG
authors.lastname: Oliver
authors.forename: Roger G
authors.initials: RG
authors.lastname: Linington
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology*; D016000:Cluster Analysis; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006090:Gram-Negative Bacteria / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000378:metabolism; D008969:Molecular Sequence Data; D009285:Naphthoquinones / Q000494:pharmacology; D012336:RNA, Ribosomal, 16S
chemical_list: D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; D012336:RNA, Ribosomal, 16S; C580877:arromycin