Basis for the extraordinary genetic stability of anthrax.

Over 500 isolates of anthrax bacillus from around the world represent one of the most genetically homogeneous microbes. There are three possibilities for this genetic stability: (1) anthrax has an extraordinarily high fidelity repair system, (2) genetic damage to anthrax is usually lethal, and/or (3) a highly demanding and selective process exists in its environment that is necessary for the completion of its life cycle. Using probes made from genes selected by growth of an Escherichia coli expression vector Bacillus anthracis library on hypertrophic high nitrate concentration medium, genes unique to B. anthracis were isolated. High nitration conditions generated stable chromosomal mutants that displayed altered morphology and life-cycle progression. Therefore, life-cycle progression connected to nitration, associated with host inflammatory response, selects for mutants that show life-cycle progression tightly coupled to progression of the inflammatory response to anthrax. Significant variation from this coupled progression leads to failure of anthrax to complete its life-cycle at the death of its host.