Draft genome sequences of Acidithiobacillus thiooxidans ATCC 19377 and A. caldus ATCC 51756 have been annotated. Bioinformatic analysis of these two new genomes, together with that of A. ferrooxidans ATCC 23270, allows the prediction of metabolic and regulatory models for each species and has provided a unique opportunity to undertake comparative genomic studies of this group of bioleaching bacteria. In this paper, we report preliminary information on metabolic and electron transfer pathways for ten characteristics of the three acidithiobacilli: CO2 fixation, the TCA cycle, sulfur oxidation, sulfur reduction, iron oxidation, iron assimilation, hydrogen oxidation, flagella formation, Che signaling (chemotaxis) and nitrogen fixation. Predicted transcriptional and metabolic interplay between pathways pinpoints potential coordinated responses to environmental signals such as energy source, oxygen and nutrient limitations. The predicted pathway for nitrogen fixation in A. ferrooxidans will be described as an example of such an integrated response. Several responses appear to be especially characteristic of autotrophic microorganisms and may have direct implications for metabolic processes of critical relevance to the understanding of how these microorganisms survive and proliferate in extreme environments, including industrial bioleaching operations.