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[log in to unmask]" type="cite">Thesis Defense Announcement
To:  The George Mason University Community


Candidate: Steve St. John
Program: Master of Science in Biology

Date:   Tuesday April 16, 2013
Time:   10:00 a.m.
Place:  George Mason University, 
	    Prince William Campus
	    Bull Run Hall, Room 253

  
Title: "Bacillus anthracis Co-Opts Nitric Oxide and Host Serum Albumin for Pathogenicity in Hypoxic Conditions"

Thesis Director: Dr. Serguei Popov

Thesis Committee:  Dr. Daniel N. Cox and Dr. Geraldine Grant
A copy of the thesis will be available in the Johnson Center Library.  All are invited to attend the defense.

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. Another toxin-independent mechanism relevant to late-stage anthrax was shown with non-phagocytic host cells exposed to pathogenic factors secreted by B. anthracis in microaerobic (hypoxic) conditions. In addition to synergistic effect of the pore-forming hemolysin (anthrolysin O) perforating the host cell and the fermentation metabolite (succinic acid) fueling the release of reactive oxygen species from mitochondria, this mechanism involves the activity of NO-derived toxic product(s). In this study we for the first time present evidence that NO produced by baNOS 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 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, which 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.


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