Updated project metadata. Antibiotic resistance is one of the major threats to human health. Combination of antibiotics with metals is among the proposed alternative treatments. However, so far only one such combination with the metal bismuth successfully used in clinics against Helicobacter pylori. This bacterial pathogen colonizes the human stomach potentially resulting in gastric cancer that causes 800,000 deaths every year. The effect of bismuth on H. pylori is not understood, for sub-lethal doses, such as those present in the plasma of treated patients. We addressed this question and observed that bismuth induces the formation of homogeneous membrane vesicles (MVs) with unique protein cargo content enriched in bismuth-binding proteins. To our surprise, MVs concentrate bismuth, unlike bacterial cells from which they originate. Our results revealed a novel function of MVs in metal detoxification where bismuth is accumulated to discard it from bacteria. Polyphosphate granules (poly-P) formed upon bismuth exposure are associated with changes in nucleoid structure and cell segregation. Thus, even low doses of bismuth induce profound changes in H. pylori physiology and highlight novel defense mechanisms employed by bacteria against bismuth toxicity.