Nanoscaled discovery of a shunt rifamycin fromSalinispora arenicolausing a three-colour GFP-taggedStaphylococcus aureusmacrophage infection assay

Abstract

AbstractAntimicrobial resistance has emerged as an urgent global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent.Staphylococcus aureusis a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival ofS. aureusin macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by GFP-taggedStaphylococcus aureusas a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a novel, active rifamycin analogue. Our findings indicate a promising new approach to the identification of anti-microbial compounds with macrophage intracellular activity. The novel antibiotic identified here may represent a useful addition to our armoury in tackling the silent pandemic of antimicrobial resistance.