An important reason for the decreased sensitivity of bacteria towards antibiotics is their capability to form so-called biofilms. The increased tolerance of sessile cells is multifactorial and includes reduced penetration rate and potency of antibiotics through dense biofilms. Strategies that have the ability to interfere with the integrity of biofilms and allowing a better penetration of antimicrobial agents are highly sought after. In this work, we explore the potential of laser-induced vapor nanobubbles (VNB) formed from plasmonic nanoparticles irradiated with nanosecond pulsed laser light to locally disturb biofilm integrity and improve antibiotics diffusion. Our results show that biofilms of both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria can be locally disrupted by the pressure waves from laser-induced VNB inside the biofilms. Most importantly, VNB-mediated biofilm disruption increased tobramycin efficacy up to 1-3 log orders of magnitude, depending on the treatment regimens and type of organism. In addition, we explored the use of VNB to enhance the efficacy of a broad range of antimicrobials used for treating wound infections, towards a first potential clinical application of the technique. Our results confirm that VNB-mediated biofilm disruption is an effective technique to enhance the activity of those antimicrobials that experience hindered diffusion in biofilms. Future work will extend the evaluation of this novel concept towards more complex multi-species biofilms and in vitro wound models before going to in vivo evaluations.
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