An essential role for bacterial nitric oxide synthase in Staphylococcus aureus electron transfer and colonization

Nitric oxide (NO center dot) is a ubiquitous molecular mediator in biology. Many signalling actions of NO center dot generated by mammalian No-center dot synthase ( NOS) result from targeting of the haem moiety of soluble guanylate cyclase. Some pathogenic and environmental bacteria also produce a NOS that is evolutionary related to the mammalian enzymes, but a bacterial haem-containing receptor for endogenous enzymatically generated NO center dot has not been identified previously. Here, we show that NOS of the human pathogen Staphylococcus aureus, in concert with an NO center dot- metabolizing flavohaemoprotein, regulates electron transfer by targeting haem-containing cytochrome oxidases under microaerobic conditions to maintain membrane bioenergetics. This process is essential for staphylococcal nasal colonization and resistance to the membrane-targeting antibiotic daptomycin and demonstrates the conservation of NOS-derived NO center dot-haem receptor signalling between bacteria and mammals.