A new strategy for battling bacterial resistance: Turning potent, non-selective and potentially non-resistance-inducing biocides into selective ones

Abstract

Antibiotic alternatives are in great need for combating antibiotic resistance. Selective delivery of a potent non-selective non-resistance-inducing biocide (C17) to MRSA was achieved by encapsulating it in solid lipid nanoparticles (SLNs) conjugated with a MRSA-specific antibody (termed as "Ab"). The C17-loaded Ab-conjugated SLNs (C17-SLN-Ab) demonstrated significantly better antimicrobial activity than its antibody free counterpart (C17-loaded SLN) and C17-loaded SLN with a non-specific IgG antibody. In a new MRSA/fibroblast co-culture assay, C17-SLN-Ab showed selective toxicity toward MRSA than fibroblast cells. C17-SLN-Ab possesses double selectivity, exhibiting higher toxicity to MRSA than to Pseudomonas aeruginosa. This same strategy was used to successfully increase C17's selectivity against E. coli K12 by switching the conjugated anti-MRSA antibody to an anti-E. coli antibody, demonstrating versatility of this new strategy. This proof-of-concept research can be extended to other non-selective antimicrobials, against which bacterial resistance is unlikely to develop, to generate a new group of promising antibiotic alternatives.

Keywords: Active targeting; Antibody; Biocide; Selective kill; Solid lipid nanoparticle.