Probiotic disruption of quorum sensing reduces virulence and increases cefoxitin sensitivity in methicillin resistant Staphylococcus aureus

Abstract

Abstract Antimicrobial resistance is a growing threat to food safety, medical advancement, and overall global health. Methicillin resistant Staphylococcus aureus (MRSA) is typically a commensal species that, given an opportunity to establish an infection, transforms into a formidable pathogen with high rates of mortality and morbidity. Therefore, it is globally recognized that new therapies to combat this pathogen are desperately needed. A potential strategy in combating MRSA resistance and infections is the development of alternative therapeutics that interfere with bacterial quorum sensing (QS) systems involved in cell-to-cell communication. QS systems are crucial in the regulation of many virulence traits in MRSA such as methicillin resistance, exotoxin and surface protein expression, antioxidant production and immune cell evasion. Based on our previous research, in which we have shown that probiotic bioactive metabolites act as novel QS-quenching compounds, we propose in this letter that the same probiotic compounds can be used in tandem with a beta-lactam antibiotic to “re-sensitize” MRSA clinical isolates to cefoxitin. Moreover, we show that these probiotic metabolites decrease production of carotenoids and alpha-hemolysin in active cultures of MRSA, resulting in reduced toxicity and diminished resistance to hydrogen peroxide cytotoxicity in vivo.