Targeted laser therapy synergistically enhances efficacy of antibiotics against multi-drug resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms

The growing prevalence of biofilm-associated multi-drug resistant (MDR) bacteria necessitates the innovation of non-traditional approaches to improve the effectiveness of mainstay antibiotics. Here, we evaluated the use of gold nanoparticle (GNP)-targeted pulsed laser therapy to enhance antibiotic efficacy against in vitro methicillin-resistant Staphylococcus aureus (MRSA) and MDR Pseudomonas aeruginosa biofilms. Treatment with antibody-conjugated GNPs followed by nanosecond-pulsed laser irradiation at 532 nm (~1.0 J/cm2) dispersed 96–99% of the biofilms relative to controls. GNP-targeted laser therapy combined with gentamicin or amikacin caused a synergistic 4- and 5-log reduction in the viability of MRSA and P. aeruginosa biofilms, respectively, whereas GNP-targeted laser therapy or antibiotics alone decreased biofilm viability by only ~1 log. Notably, GNP-targeted laser therapy was able to increase the antibiotic susceptibility of the biofilms to the level of drug sensitivity observed in planktonic MRSA and P. aeruginosa cultures, further indicating effective biofilm dispersal via this novel approach. Pulsed laser-induced photothermal destruction of biofilms is a promising approach for improving the activity of antibiotics against recalcitrant bacterial infections. We have developed a gold nanoparticle (GNP)-targeted pulsed laser therapy that can rapidly disperse 96–99% of biofilms and kill up to ~90–98% of the biofilm-associated bacteria. Furthermore, GNP-targeted laser therapy combined with antibiotics caused a 4- to 5-log reduction in MRSA and Pseudomonas aeruginosa biofilm viability, whereas antibiotics alone resulted in only a 1-log decrease in viability. These results lay the foundation for nanoparticle-targeted laser therapies as adjuvants to improve the efficacy of mainstay antibiotics. [Display omitted]