USMB-induced synergistic enhancement of aminoglycoside antibiotics in biofilms.
This study evaluated the effect of combining antibiotics with ultrasound and microbubbles (USMB) toward the eradication of biofilms. Pseudomonas aeruginosa PAO1 biofilms were treated with the antibiotics gentamicin sulfate or streptomycin sulfate, or a combination of USMB with the respective antibiotics. Biofilm structure was quantified using confocal laser scanning microscopy with COMSTAT analysis, while activity was measured as whole-biofilm CO2 production in a continuous-flow biofilm model. The combined antibiotic-USMB treatment significantly impacted biofilm biomass, thickness and surface roughness compared to antibiotics alone (p<0.05). USMB exposure caused the formation of craters (5-20μm in diameter) in the biofilms, and when combined with gentamicin, activity was significantly lower, compared to gentamicin, USMB or untreated controls, respectively. Interestingly, the CO2 production rate following combined streptomycin-USMB treatment was higher than after streptomycin alone, but significantly lower than USMB alone and untreated control. These results show strong evidence of a synergistic effect between antibiotics and USMB, although the varied response to different antibiotics emphasize the need to optimize the USMB exposure conditions to maximize this synergism and ultimately transfer this technology into clinical or industrial practice.
Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada.
Evan
E
Ronan
Department of Physics, Ryerson University, Toronto, Ontario, Canada.
Narbeh
N
Edjiu
Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada.
Otini
O
Kroukamp
Department of Chemistry and Biology, Ryerson University, Toronto, Ontario, Canada.
Gideon
G
Wolfaardt
Department of Physics, Ryerson University, Toronto, Ontario, Canada. Electronic address: karshafian@ryerson.ca.
Raffi
R
Karshafian
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development* / Q000528:radiation effects; D003131:Combined Modality Therapy / Q000379:methods; D004357:Drug Synergism; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000528:radiation effects; D005839:Gentamicins / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D013307:Streptomycin / Q000494:pharmacology; D016896:Treatment Outcome; D014464:Ultrasonic Therapy; D000069453:Ultrasonic Waves
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005466:Fluorocarbons; D005839:Gentamicins; D013307:Streptomycin; C042852:perflutren
Antibiotics; Biofilm; Inertial cavitation; Ultrasound and microbubble bioeffects