Bacterial thiopurine methyltransferases (bTPMTs) can favour resistance towards toxic tellurite oxyanions through a pathway leading to the emission of a garlic-like smell. Gene expression profiling completed by genetic, physiological and electron microscopy analyses was performed to identify key bacterial activities contributing to this resistance process. Escherichia coli strain MG1655 expressing the bTPMT was used as a cell model in these experiments. This strain produced a garlic-like smell which was found to be due to dimethyl telluride, and cell aggregates in culture media supplemented with tellurite. Properties involved in aggregation were correlated with cell attachment to polystyrene, which increased with tellurite concentrations. Gene expression profiling supported a role of adhesins in the resistance process with 14% of the tellurite-regulated genes involved in cell envelope, flagella and fimbriae biogenesis. Other tellurite-regulated genes were, at 27%, involved in energy, carbohydrate and amino acid metabolism including the synthesis of antioxidant proteins, and at 12% in the synthesis of transcriptional regulators and signal transduction systems. Escherichia coli mutants impaired in tellurite-regulated genes showed ubiquinone and adhesins synthesis, oxidative stress response, and efflux to be essential in the bTPMT resistance process. High tellurite resistance required a synergistic expression of these functions and an efficient tellurium volatilization by the bTPMT.