Anthrax toxins and the host: a story of intimacy

Although the dramatic events of the year 2001 have revitalized the interest in anthrax, research on Bacillus anthracis and its major virulence factors is one of the oldest theme in microbiology and started with the early works of Robert Koch and Louis Pasteur. The anthrax toxins are central to anthrax pathogenesis. They were discovered in the mid-1950s and since then there has been an enormous amount of work to elucidate both the molecular and physiopathological details of their mode of action. In this review, after a brief introduction of B. anthracis, we will focus on the latest findings that concern two aspects of anthrax toxin research: the environmental signals and the molecular mechanisms that regulate toxin synthesis, and the mechanisms of intoxication. We hope to convince the reader that the anthrax toxins are highly specialized determinants of B. anthracis pathogenicity: their synthesis is integrated within a global virulence programme and they target key eukaryotic cell proteins. We conclude with a consideration of the therapeutic perspectives arising from our current knowledge of how the toxins work.