title: Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages.
abstract: Phagocytes generate nitric oxide (NO) and other reactive oxygen and nitrogen species in large quantities to combat infecting bacteria. Here, we report the surprising observation that in vivo survival of a notorious pathogen-Bacillus anthracis-critically depends on its own NO-synthase (bNOS) activity. Anthrax spores (Sterne strain) deficient in bNOS lose their virulence in an A/J mouse model of systemic infection and exhibit severely compromised survival when germinating within macrophages. The mechanism underlying bNOS-dependent resistance to macrophage killing relies on NO-mediated activation of bacterial catalase and suppression of the damaging Fenton reaction. Our results demonstrate that pathogenic bacteria use their own NO as a key defense against the immune oxidative burst, thereby establishing bNOS as an essential virulence factor. Thus, bNOS represents an attractive antimicrobial target for treatment of anthrax and other infectious diseases.
authors.affiliation: Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shatalin
authors.forename: Ivan
authors.initials: I
authors.lastname: Gusarov
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Avetissova
authors.forename: Yelena
authors.initials: Y
authors.lastname: Shatalina
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: McQuade
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nudler
mesh_terms: D000818:Animals; D000881:Anthrax / Q000378:metabolism / Q000473:pathology; D001408:Bacillus anthracis / Q000472:pathogenicity*; D002460:Cell Line; D002470:Cell Survival; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D015996:Survival Rate; D013997:Time Factors; D014774:Virulence
chemical_list: D009569:Nitric Oxide