The nitric oxide paradox: antimicrobial and inhibitor of antibiotic efficacy

It is well-known that antibiotics target energy-consuming processes and a significant body of research now supports the conclusion that the metabolic state of bacteria can have a profound impact upon the efficacy of antibiotics. Several articles implicate bacterial energetics and the respiratory inhibitor nitric oxide (NO) in this process, although pinpointing the precise mechanism for how NO can diminish the potency of a range of antibiotics through modulating bacterial energy metabolism has proved challenging. Herein, we introduce the role of NO during infection, consider known links between NO and antibiotic efficacy, and discuss potential mechanisms via which NO present at the site of infection could mediate these effects through controlling bacterial energetics. This perspective article highlights an important relationship between NO and antibiotic action that has largely been overlooked and outlines future considerations for the development of new drugs and therapies that target bacterial energy metabolism.