ε-Polylysine Nanoconjugates: Value-Added Antimicrobials for Drug-Resistant Bacteria.

Abstract

Antimicrobial resistance poses a serious threat to human health and is evidently not restricted to any one part of the globe. Over the last few decades, no new antibiotics have been discovered, and many antibiotics currently available are failing against several critical pathogenic strains due to emerging drug resistance. We have designed a strategy to combat deadly drug-resistant bacteria by using nanocargos that consist of gold nanoparticles (AuNPs) conjugated to ε-polylysine (PLL) and octadecanethiol (C18) either alone or in combination. These nanocargos when tested against reference strains of carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA) showed 15-20-fold higher antibacterial activity compared to free PLL. The minimum inhibitory concentration (MIC) of the nanoconjugates was found to lie between 8 and 15 μg/mL for both these bacteria, and they were also found to be nonhemolytic and nontoxic to mammalian cells. The mechanistic evaluation of antibacterial action showed alternate pathways of uptake for free PLL and the nanoconjugates. Further, the nanocargos were successfully used and found to be superior to free PLL in preventing biofilm formation in MRSA and CRAB. The PLL nanoconjugates may find applications in prevention of bacterial biofilm formation on surfaces such as surgical instruments and indwelling devices like stents, catheters, cannulas, orthopedic implants, and pacemakers.