Bacillus anthracis-derived nitric oxide induces protein S-nitrosylation contributing to macrophage death
详细信息 查看全文
- 作者：Myung-Chul Chung ; mchung3@gmu.edu ; Aarthi Narayanan ; Taissia G. Popova ; Fatah Kashanchi ; Charles L. Bailey ; Serguei G. Popov
- 关键词：bNO ; B.anthracis-derived nitric oxide ; bNOS ; bacterial nitric oxide synthase ; BST ; biotin-switch technique ; LT ; lethal toxin ; ET ; edema toxin ; ETC ; electron transfer complexes ; ROS ; reactive oxygen species ; L-NAME ; N¦Ø-nitro-l-arginine methyl ester ; MOI
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2013
- 出版时间：4 January, 2013
- 年：2013
- 卷：430
- 期：1
- 页码：125-130
- 全文大小：594 K
文摘
Bacillus anthracis, a causative agent of anthrax, is able to germinate and survive within macrophages. A recent study suggested that B. anthracis-derived nitric oxide (bNO) is a key aspect of bacterial defense that protects bacterial DNA from oxidative burst in the macrophages. However, the virulent effect of bNO in host cells has not been investigated. Here, we report that bNO contributes macrophage killing by S-nitrosylation of bioenergetic-relating proteins within mitochondria. Toxigenic Sterne induces expression of the bnos gene and produces bNO during early stage of infection. Nitroso-proteomic analysis coupled with a biotin-switch technique demonstrated that toxigenic infection induces protein S-nitrosylation in B. anthracis-susceptible RAW264.7. For each target enzyme tested (complex I, complex III and complex IV), infection by B. anthracis Sterne caused enzyme inhibition. N¦Ø-nitro-l-arginine methyl ester, a NO synthase inhibitor, reduced S-nitrosylation and partially restored cell viability evaluated by intracellular ATP levels in macrophages. Our data suggest that bNO leads to energy depletion driven by impaired mitochondrial bioenergetic machinery that ultimately contributes to macrophage death. This novel mechanism of anthrax pathogenesis may offer specific approach to the development of therapeutics.