The overarching theme of this long-standing project is both a comprehensive and indepth understanding of the biology of arsenic, the most pervasive environmental toxicsubstance and carcinogen in nature. The Environmental Protection Agency calls arsenicthe most prevalent environmental toxin and carcinogen in the United States(http://www.atsdr.cdc.gov/cercla/07list.html). Arsenic causes cardiovascular andperipheral vascular diseases, neurological disorders, diabetes mellitus and various formsof cancer such as skin and bladder cancer. We have described steps in the biogeocyclefor inorganic arsenic and identified a parallel biocycle for organoarsenicals. Wehypothesize that members of microbial communities synthesize methylarsenite (MAs(III))by methylation of inorganic arsenite (As(III)) and use this extremely toxicorganoarsenical as an antibiotic against other bacteria. Man has created even moretoxic synthetic organoarsenicals for use as herbicides and antimicrobial growthpromoters. In response to environmental pressures, bacteria evolved resistancemechanisms against both biological and synthetic toxic organoarsenicals. Our overallgoal is to characterize the pathway of arsenic methylation and detoxification at thefunctional, mechanistic and structural levels. We propose three specific aims: 1)synthesis of MAs(III), 2) breakdown of MAs(III) and 3) efflux of MAs(III). We unify thesephysiological functions in a new and novel hypothesis on the evolution of antibiotics.
