This abstract was selected by our Scientific Committee to pitch on the programme in the R2B session (PM).
The hindered penetration of antibiotics through biofilms is one of the reasons why bacterial tolerance to antibiotics has risen dangerously in the past decade. Innovative approaches aiming to get rid of biofilms are required to prevent a true post-antibiotic era. One strategy is interfering with the dense biofilm architecture in order to enhance antibiotic flux towards the deeper cell layers in biofilms. Here, we aimed to locally interfere with the biofilm integrity and improve diffusion of antimicrobials by nanoscale laser-induced bubbles formed around plasmonic nanoparticles created deep within the biofilm. Our results show that small cationic AuNP can migrate deep into cell clusters of both gram-negative as gram-positive biofilms and that subsequent laser irradiation results in formation of vapour nanobubbles (VNB) inside these clusters. The mechanical force of the expanding bubbles could subtly but significantly expand the space between sessile cells, thereby increasing antibiotics efficiency up to 1-3 log orders of magnitude, depending on the organism and treatment conditions. Importantly, even though substantial cluster disruption occurred upon VNB formation, no bacteria were found to have dispersed into the environment, thereby circumventing life-threatening systemic spread. To evaluate potential clinical application of this new approach, we explored the potential of VNB to enhance the potency of antimicrobials commonly used to treat biofilm related wound infections. Our results showed that the formation of VNB can resolve the diffusion barrier in biofilms, as VNB pre-treatment enhanced the efficacy of those antimicrobials that experienced hindered biofilm diffusion. While further work is needed to evaluate this concept in vivo, we can conclude that laser-induced VNB are an efficient way to enhance drug penetration deep into biofilms, and pave the way towards clinical translation of this novel approach for the treatment of wound infections.