Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1009-13. doi: 10.1073/pnas.0710950105. Epub 2008 Jan 22.

Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages.

Author information

1
Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.

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.

PMID:
18215992
PMCID:
PMC2242674
DOI:
10.1073/pnas.0710950105
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center