title: Activity of novel inhibitors of Staphylococcus aureus biofilms.
abstract: Staphylococcus aureus is one of the most important pathogens causing chronic biofilm infections. These are becoming more difficult to treat owing to drug resistance, particularly because S. aureus biofilms limit the efficacy of antimicrobial agents, leading to high morbidity and mortality. In the present study, we screened for inhibitors of S. aureus biofilm formation using a natural product library from the Korea Chemical Bank (KCB). Screening by crystal violet-based biomass staining assay identified hit compounds. Further examination of antibiofilm properties of these compounds was conducted and led to the identification of celastrol and telithromycin. In vitro, both celastrol and telithromycin were toxic to planktonic S. aureus and also active against a clinical methicillin-resistant S. aureus (MRSA) isolate. The effect of the compounds on preformed biofilms of clinical MRSA isolates was evaluated by confocal laser scanning microscopy (CLSM), which revealed the absence of typical biofilm architecture. In addition, celastrol and telithromycin inhibited the production of extracellular protein at selected sub-MIC concentrations, which revealed the reduced extracellular polymeric substance (EPS) secretion. Celastrol exhibited greater cytotoxicity than telithromycin. These data suggest that the hit compounds, especially telithromycin, could be considered novel inhibitors of S. aureus biofilm. Although the mechanisms of the effects on S. aureus biofilms are not fully understood, our data suggest that telithromycin could be a useful adjuvant therapeutic agent for S. aureus biofilm-related infections.
authors.affiliation: Department of Medical Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea.
authors.forename: Seung-Gyun
authors.initials: SG
authors.lastname: Woo
authors.affiliation: Department of Medical Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea.
authors.forename: So-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea.
authors.forename: Kyoung-Hee
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Ha
authors.affiliation: Department of Medical Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea. omnibin@sch.ac.kr.|Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea. omnibin@sch.ac.kr.
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Eom
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D001688:Biological Products / Q000494:pharmacology; D005840:Gentian Violet; D057166:High-Throughput Screening Assays; D048628:Ketolides / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D008826:Microbial Sensitivity Tests; D053978:Pentacyclic Triterpenes; D010933:Plankton / Q000187:drug effects / Q000254:growth & development; D054852:Small Molecule Libraries / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D048628:Ketolides; D053978:Pentacyclic Triterpenes; D054852:Small Molecule Libraries; D014315:Triterpenes; D005840:Gentian Violet; C106791:telithromycin; C050414:celastrol