title: An essential role for bacterial nitric oxide synthase in Staphylococcus aureus electron transfer and colonization.
abstract: Nitric oxide (NO•) is a ubiquitous molecular mediator in biology. Many signalling actions of NO•generated by mammalian NO•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•has not been identified previously. Here, we show that NOS of the human pathogen Staphylococcus aureus, in concert with an NO•-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•-haem receptor signalling between bacteria and mammals.
authors.affiliation: Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.
authors.forename: Traci L
authors.initials: TL
authors.lastname: Kinkel
authors.affiliation: Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.
authors.forename: Smirla
authors.initials: S
authors.lastname: Ramos-Montañez
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Pando
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Tadeo
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.
authors.forename: Erin N
authors.initials: EN
authors.lastname: Strom
authors.affiliation: Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Libby
authors.affiliation: Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.|Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195-7735, USA.
authors.forename: Ferric C
authors.initials: FC
authors.lastname: Fang
mesh_terms: D000332:Aerobiosis; D000818:Animals; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009296:Nasal Cavity / Q000382:microbiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D019001:Nitric Oxide Synthase; D003576:Electron Transport Complex IV