Mercury (Hg), one of the most toxic and widely distributed heavy metals, has a high affinity for thiol groups. Thiol groups reduce and sequester Hg. Therefore, low molecular weight and protein thiols may be important cell components used in Hg resistance. To date, the role of low molecular weight thiols in Hg-detoxification remains understudied. The mercury resistance () operon of suggests an evolutionary link between Hg(II) resistance and low molecular weight thiol metabolism. This operon encodes for an enzyme involved in methionine biosynthesis, Oah. Challenge with Hg(II) resulted in increased expression of genes involved in the biosynthesis of multiple low molecular weight thiols (cysteine, homocysteine, and bacillithiol), as well as the thioredoxin system. Phenotypic analysis of gene replacement mutants indicated that Oah contributes to Hg resistance under sulfur limiting conditions, and strains lacking bacillithiol and/or thioredoxins are more sensitive to Hg(II) than the wild type. Growth in presence of either a thiol oxidizing agent or a thiol alkylating agent increased sensitivity to Hg(II). Furthermore, exposure to 3 μM Hg(II) consumed all intracellular reduced bacillithiol and cysteine. Database searches indicate that is present in all spp. operons. The presence of a thiol related gene was also detected in some alphaprotobacterial operons, in which a glutathione reductase gene was present, supporting the role of thiols in Hg(II) detoxification. These results have led to a working model in which LMW thiols act as Hg(II) buffering agents while Hg is reduced by MerA.The survival of microorganisms in presence of toxic metals is central to life's sustainability. The affinity of thiol groups to toxic heavy metals drives microbe-metal interactions and modulate metal toxicity. Mercury detoxification () genes likely originated early in microbial evolution among geothermal environments. Little is known about how systems interact with cellular thiol systems. spp. possess a simple operon in which a low molecular weight thiol biosynthesis gene is present, along with and In this study, we present experimental evidence for the role of thiol systems in mercury resistance. Our data suggest that in thiolated compounds may function side-by-side with genes to detoxify mercury. Thus, thiol systems function in consort with-mediated resistance to mercury, suggesting exciting new questions for future research.