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

Shatalin, K. et al., Proc Natl Acad Sci U S A 105 (3), 1009 (2008).

Speaker: Kai-yun Lu (呂凱筠)                                       Time: 15:00~16:00, Apr. 16, 2008

Commentator: Dr. Lien-I Hor (何漣漪老師)          Place: Room 601

Abstract:

     Bacillus anthracis , the sopre - producing soil organism , causes acute life - threatening infections in humans and domestic animals .¹  Although the innate immune response combat infecting B. anthracis , the mechanism evades immune attack remains not clearly understood. Previous work by the authors had demonstrated that nonpathogenic B. subtilis utilized its own nitric  oxide   (NO)   to  defend  sudden  oxidative  stress  by  preventing  Fenton reaction  and  activating  catalase  directly . ²   Because  B. anthracis  and  B. subtilis  are  closed  relatives  ,  the  authors  started  to investigate  the  role  of  bacterial NO in its pathogenicity .  In this research , they analyzed the effect of mutation in bacterial  NO – synthase  (bNOS)  on oxidative stress response , and revealed that  in vivo  survival of B. anthracis critically depended on bNOS activity. In A/J mouse model of systemic infection, bNOS mutant strain lost their virulence, with a dramatic LD50 increase compared with wild – type strain; and exhibited compromised survival when germinating within macrophages. They also suggested that bNOS – derived NO protected B. anthracis chromosome from macrophage induced Fenton reaction at the early stage of infection .  Based on these observations , this article suggests that pathogenic bacteria produce their own NO by bNOS for rapid protection from immune oxidative attack . Thus , bNOS–specific inhibitor can be designed for treatment of anthrax and other infectious diseases.

References:

1.      Mock, M. and Fouet, A., Anthrax. Annu Rev Microbiol 55, 647 (2001).

2.      Gusarov, I. and Nudler, E., NO-mediated cytoprotection: instant adaptation to oxidative stress in bacteria. Proc Natl Acad Sci U S A 102 (39), 13855 (2005).