title: Novel pentadecenyl tetrazole enhances susceptibility of methicillin-resistant Staphylococcus aureus biofilms to gentamicin.
abstract: One method that bacteria employ to reduce their susceptibility to antibiotics is the formation of biofilms. We developed a robust 6-well plate biofilm assay to evaluate early-stage discovery compounds against methicillin-resistant Staphylococcus aureus (MRSA). Tissue culture-treated 6-well plates were selected for this assay because they facilitate the adherence of MRSA and enable accurate determination of the number of CFU in each well. The MRSA biofilms formed in this assay exhibit increased tolerances to clinically used antibiotics. Using this biofilm assay, we identified a novel potentiator of gentamicin against MRSA biofilms. The combination of gentamicin and pentadecenyl tetrazole is superior to clinically used MRSA antibiotics against these MRSA biofilms. This novel combination also exhibits synergistic effects on MRSA planktonic cells. This plant-derived compound reveals promise for its effectiveness and warrants further lead optimization as an antibiotic and aminoglycoside potentiator.
authors.affiliation: Sequoia Sciences, 1912 Innerbelt Business Center Drive, St. Louis, MO 63114, USA. kolson@sequoiasciences.com
authors.forename: Krista M
authors.initials: KM
authors.lastname: Olson
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Starks
authors.forename: Russell B
authors.initials: RB
authors.lastname: Williams
authors.forename: Mark
authors.initials: M
authors.lastname: O'Neil-Johnson
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Ellis
authors.forename: John E
authors.initials: JE
authors.lastname: Reilly
authors.forename: Gary R
authors.initials: GR
authors.lastname: Eldridge
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion; D018441:Biofilms / Q000187:drug effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: C569660:5-(pentadec-8-enyl)-2H-tetrazole; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D013777:Tetrazoles