title: Marine-derived quorum-sensing inhibitory activities enhance the antibacterial efficacy of tobramycin against Pseudomonas aeruginosa.
abstract: Bacterial epiphytes isolated from marine eukaryotes were screened for the production of quorum sensing inhibitory compounds (QSIs). Marine isolate KS8, identified as a Pseudoalteromonas sp., was found to display strong quorum sensing inhibitory (QSI) activity against acyl homoserine lactone (AHL)-based reporter strains Chromobacterium violaceum ATCC 12472 and CV026. KS8 supernatant significantly reduced biofilm biomass during biofilm formation (-63%) and in pre-established, mature P. aeruginosa PAO1 biofilms (-33%). KS8 supernatant also caused a 0.97-log reduction (-89%) and a 2-log reduction (-99%) in PAO1 biofilm viable counts in the biofilm formation assay and the biofilm eradication assay respectively. The crude organic extract of KS8 had a minimum inhibitory concentration (MIC) of 2 mg/mL against PAO1 but no minimum bactericidal concentration (MBC) was observed over the concentration range tested (MBC > 16 mg/mL). Sub-MIC concentrations (1 mg/mL) of KS8 crude organic extract significantly reduced the quorum sensing (QS)-dependent production of both pyoverdin and pyocyanin in P. aeruginosa PAO1 without affecting growth. A combinatorial approach using tobramycin and the crude organic extract at 1 mg/mL against planktonic P. aeruginosa PAO1 was found to increase the efficacy of tobramycin ten-fold, decreasing the MIC from 0.75 to 0.075 µg/mL. These data support the validity of approaches combining conventional antibiotic therapy with non-antibiotic compounds to improve the efficacy of current treatments.
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK. a.busetti@qub.ac.uk.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Busetti
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK. gshaw08@qub.ac.uk.
authors.forename: George
authors.initials: G
authors.lastname: Shaw
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK. j.megaw@qub.ac.uk.
authors.forename: Julianne
authors.initials: J
authors.lastname: Megaw
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK. s.gorman@qub.ac.uk.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
authors.affiliation: School of Biological Sciences, Medical Biology Center, 97 Lisburn Road, Belfast BT9 7BL, UK. c.maggs@qub.ac.uk.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Maggs
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK. b.gilmore@qub.ac.uk.
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Gilmore
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms; D002861:Chromobacterium / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D031161:Pseudoalteromonas / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D053038:Quorum Sensing / Q000187:drug effects*; D012623:Seawater / Q000382:microbiology; D014031:Tobramycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin