(168d) Photoexcited Quantum Dots Potentiate Antibiotic Activity in Multidrug-Resistant Bacteria

Authors: 
Courtney, C., University of Colorado Boulder
Nagpal, P., University of Colorado Boulder
Chatterjee, A., University of Colorado Boulder
Goodman, S., University of Colorado Boulder
Li, F., University of Colorado Boulder
Madinger, N., University of Colorado
The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics being developed. In order to treat MDR infections, new classes of antibiotics must be developed that are effective against already pervasive MDR infections. While current antibiotics are derived from natural products, investigating true synthetic antibiotics provides opportunity to design therapeutics for antimicrobial targets of interest. In this study we present a novel, nanoparticle based therapeutic that is able to inhibit MDR clinical isolates of Escherichia coli, Salmonella typhimurium, and Klebsiella pneumoniae both as a monotherapy as well as combination therapy with antibiotics that the isolates were previously resistant against. The nanoparticles used in this study generate specific, light activated reactive species (LARS) which alter the drug resistance phenotype and lower the level of resistance of the clinical strains to traditional antibiotics. We show that the redox homeostasis perturbing nanoparticles in combination with protein synthesis inhibiting antibiotics, namely chloramphenicol, streptomycin, and clindamycin, lower the IC50 of resistant MDR clinical isolates below the Clinical Laboratory Standards Institute (CLSI) breakpoint. We find that this phenomenon is not only limited to protein synthesis inhibiting antibiotics, but extends to other classes of antibiotics such as fluoroquinolones. Using a multiplicative model, we show that this combination therapeutic effect is additive and the effect is concentration dependent on both the antibiotic as well as the nanoparticle concentration. Interestingly the nanoparticle is able to have this drastic effect on antibiotic resistance at nanomolar concentrations highlighting the strong effect of the LARS produced. The bactericidal effect of the combination therapy is greater than that of each mono-therapy alone highlighting the potential utility of this combination therapy for treating MDR infections.