Marine-Derived Quorum-Sensing Inhibitory Activities Enhance the Antibacterial Efficacy of Tobramycin against Pseudomonas aeruginosa

Marine Drugs

Alessandro Busetti²  George Shaw²  Julianne Megaw²  Sean P. Gorman²  Christine A. Maggs¹  Brendan F. Gilmore² 

[1] School of Biological Sciences, Medical Biology Center, 97 Lisburn Road, Belfast BT9 7BL, UK; E-Mail:;School of Pharmacy, Queen’s University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, UK; E-Mails:

关键词: antibiotic resistance;    antimicrobial synergy;    quorum sensing inhibitors;    marine bacteria;    biofilm;    marine biodiscovery;    tobramycin;    Pseudomonas aeruginosa;   

DOI  :  10.3390/md13010001

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.