Bismuth is a heavy metal that is relatively non-toxic to humans in comparison to the metals and metalloids surrounding it in the periodic table (i.e. polonium, tellurium, antimony, tin, and lead). However, bismuth is toxic to many prokaryotes, and bismuth compounds have been used for more than 200 years to treat ailments such as syphilis, diarrhea resulting from bacterial infections (bismuth subsalicylate is the active ingredient in Pepto-Bismol), and peptic ulcers caused by Helicobacter pylori (reviewed by Briand and Burford, 1999). About half of the bismuth mined each year is used in pharmaceuticals, with the remainder used in other products such as cosmetics, semiconductors, glass and ceramics, and hunting ammunition. The majority of research investigating microbial interactions with bismuth has focused on bismuth toxicity. Other recent reports have described the production of trimethylbismuth by anaerobic bacteria and methanogens (reviewed by Bentley and Chasteen, 2002) and the interaction of bismuth ions with microbial heavy metal and metalloid resistance systems.

Bismuth toxicity in prokaryotes is not completely understood. Proposed mechanisms include disruption of the cell wall (Stratton et al, 1999), enzyme inhibition (reviewed by Sadler et al, 1999), and interference with iron transport (Domenico et al, 1996). Toxicological studies have revealed bismuth accumulation associated with the cell walls of some Gram-negative bacteria (Nadeau et al, 1992; Stoltenberg et al, 2001). Nadeau et al and Marshall et al (1989) also reported the formation of reflective metallic halos around filter paper soaked with bismuth salts placed on the surface of plate cultures of various bacteria. These "bismuth mirrors" were proposed to be composed of reduced metallic bismuth, but this has not been confirmed.

Bi³⁺ ions can induce arsenical resistance operons in Gram-positive (Ji and Silver, 1991) and Gram-negative bacteria (Wu and Rosen, 1993), and the cadmium resistance operon in Staphylococcus aureus (Yoon et al, 1991). Direct interaction of Bi³⁺ with the regulatory protein of the cadmium resistance operon has been demonstrated (Busenlehner et al, 2002). However, none of the resistance systems induced by Bi³⁺ have been shown to mediate bismuth resistance, and no genes associated with bismuth resistance have been identified.

Bi³⁺ ions are known to have a high affinity for thiol ligands, and binding of Bi³⁺ by glutathione and cysteine has been described (Burford et al, 2003). Bi³⁺ ions were found to induce synthesis of glutathione-dervied metal-binding peptides ("phytochelatins") in Schizosaccharomyces pombe (Grill et al, 1986). Metallothionein synthesis can be induced by Bi³⁺ in mammalian cells (Kaji et al, 1994) and metallothioneins have been shown to bind Bi³⁺ (Sun et al, 1999).

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Grill E, Winnacker E-L, Zenk MH. Synthesis of seven different homologous phytochelatins in metal-exposed Schizosaccharomyces pombe cells. FEBS Lett. 1986,197:115-120.

Sadler PJ, Li H, Sun H. Coordination chemistry of metals in medicine: target sites for bismuth. Coord Chem Rev. 1999;185-186:689-709.