Gold nanoclusters augment a fluoroquinolone lethality against biofilm associated persister cells

Abstract

Persister cells are an important medical concern, leading to the overuse of antibiotics and ultimately contributing to antimicrobial resistance. The use of an adjuvant that augments the antibiotic efficacy has yet to be explored for combating persister cells within biofilm infections. Here we demonstrate a paradigm shift in targeting bacteria in chronic infections by coadministration of a conventional antibiotic with a novel engineered gold nanocluster (AuNC@CPP). AuNC@CPP was found to reduce the minimum biofilm eradication concentration (MBEC) of ofloxacin up to 300-fold (from > 3000 μg/mL to 10 μg/mL). Compared to ofloxacin alone (FLOXIN®Otic), coadministration of ofloxacin with AuNC@CPP induces up to a 10,000-fold reduction in bacterial burden in a validated mouse model of chronic P. aeruginosa of ear infection mimicking chronic suppurative otitis media. The biocompatibility of AuNC@CPP encourages efforts for development as an antibiotic adjunct for combating bacterial biofilm infections.