Abstract
Bacillus anthracis is a dangerous pathogen of humans and many animal species. Its virulence has been mainly attributed to the production of Lethal and Edema toxins as well as the antiphagocytic capsule. Recent data indicate that the nitric oxide (NO) synthase (baNOS) plays an important pathogenic role at the early stage of disease by protecting bacteria from the host reactive species and S-nytrosylating the mitochondrial proteins in macrophages. In this study we for the first time present evidence that bacteria-derived NO participates in the generation of highly reactive oxidizing species which could be abolished by the NOS inhibitor L - NAME, free thiols, and superoxide dismutase but not catalase. The formation of toxicants is likely a result of the simultaneous formation of NO and superoxide leading to a labile peroxynitrite and its stable decomposition product, nitrogen dioxide. The toxicity of bacteria could be potentiated in the presence of bovine serum albumin. This effect is consistent with the property of serum albumin to serves as a trap of a volatile NO accelerating its reactions. Our data suggest that during infection in the hypoxic environment of pre-mortal host the accumulated NO is expected to have a broad toxic impact on host cell functions.
Highlights
Bacillus anthracis is the causative agent of anthrax
In this study we further elucidated the recently discovered mechanism of B. anthracis toxicity toward the host cells which requires a hypoxic environment for bacterial growth and an accumulation of acidic metabolic products (Popova et al, 2011)
We show that B. anthracis was able to generate micromolar concentrations of nitric oxide (NO) in the process sensitive to the baNOS inhibitor, L-NAME
Summary
Bacillus anthracis is the causative agent of anthrax. B. anthracis spores are internalized by resident phagocytes (alveolar macrophages or dendritic cells) and transported to the regional lymph nodes (Dixon et al, 2000; Guidi-Rontani, 2002). Some internalized spores survive a bactericidal environment and initiate disease by escaping the macrophages (Cote et al, 2008). Bacterium produces several virulence factors including the toxins, such as the Lethal Toxin (LT) and Edema Toxin (ET), and a poly-γ-D-glutamic acid capsule [reviewed in Moayeri and Leppla (2009) and Guichard et al (2012)]. Accumulated evidence demonstrates that LT and ET influence many important cellular processes including the host’s innate immune response; mechanisms by which B. anthracis kills the host are not fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
