title: Bioinformatic evaluation of the secondary metabolism of antistaphylococcal environmental bacterial isolates.
abstract: The increasing occurrence of drug-resistant Staphylococcus aureus is exacerbated with a declining rate of antibiotic discovery, particularly those with new mechanisms of action. The decline in antibiotic discovery from traditional sources, such as soil actinobacteria, necessitates examination of lesser studied microbes. Here, we present a strategy to select for organisms that may have a propensity to result in new antistaphylococcal agents by using S. aureus as a bait organism, and selecting organisms that have a natural lytic activity towards it. We have isolated over 80 environmental isolates and typed these organisms using 16S rDNA sequence comparison and deployed bioinformatics to assess the secondary metabolic potential of the isolated antistaphylococcal bacteria using genomic sequences. Bioinformatic analysis highlights the enriched and unique suite of potential antibiotic polyketides and nonribosomal peptides and lantibiotic gene clusters from these organisms. Profiling organic microbial extracts further showed that many of the organisms from the 10 staphylolytic genera secrete agents with antistaphylococcal activity and may serve as new sources for future antistaphylococcal drug discovery.
authors.affiliation: Michael G. Degroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, Department of Chemistry and Chemical Biology, McMaster University, 1200 Main Street W, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Wyatt
authors.forename: Jonghyun
authors.initials: J
authors.lastname: Lee
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Ahilan
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Magarvey
mesh_terms: D039903:Actinobacteria / Q000302:isolation & purification / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics; D055808:Drug Discovery / Q000379:methods*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004783:Environmental Microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S