Nanoparticles as antibiotic-delivery vehicles (ADVs) overcome resistance by MRSA and other MDR bacterial pathogens: the grenade hypothesis

OBJECTIVES The aim of this study was to examine how the concentrated delivery of less-effective antibiotics, such as the β-lactam penicillin-G, by linkage to nanoparticles (NPs) could influence the killing efficiency against various pathogenic bacteria including methicillin-resistant-Staphylococcus aureus (MRSA) and other multi-drug resistant (MDR) strains. METHODS The β-lactam antibiotic penicillin-G (PenG) was passively-sorbed to fluorescent polystyrene NPs (20 nm) that were surface-functionalized with either carboxylic acid- (COO--NPs) or sulfate-groups (SO4--NPs) to form PenG- NPs complex. Antimicrobial activities of PenG-NPs were evaluated against Gram-negative and Gram-positive bacteria, including antibiotic resistant strains. Disc-diffusion, microdilution assays and Live/Dead staining were performed for antibacterial assessments. RESULTS The results showed that bactericidal activities of PenG- NPs complexes were statistically significantly (P < 0.05) enhanced against Gram-negative and Gram-positive strains, including MRSA and MDR strains. Fluorescence imaging verified that NPs co-migrated with antibiotics throughout clear zones of MIC agar-plate assays. The increased bactericidal abilities of NP-linked antibiotics are hypothesized to result from the greatly-increased densities of antibiotic delivered by each NP to a given bacterial cell (compared with solution concentrations of antibiotic), which overwhelms the bacterial resistance mechanism(s). CONCLUSIONS As a whole, PenG- NPs complexation demonstrated a remarkable activity against different pathogenic bacteria including MRSA and MDR strains. We term this the "grenade hypothesis". Further testing and development of this approach will provide validation of the potential usefulness for controlling antibiotic-resistant bacterial infections.