RESISTANCE TO BISMUTH AMONG GRAM-NEGATIVE BACTERIA IS DEPENDENT UPON IRON AND ITS UPTAKE

Bismuth antimicrobial action is poorly understood. Many trivalent meta ls possess antibacterial activity, especially under low iron condition s. Protection of bacteria from the deleterious effects of bismuth and other trivalent metals was demonstrated in iron-fortified media. Near- equimolar quantities of Fe3+ neutralized the growth-inhibitory effects of 250 mu M Bi3+. Resistance to bismuth action also depended on the p roduction of virulence-related siderophores. Escherichia coli, Aeromon as hydrophila or Pseudomonas aeruginosa producing aerobactin, amonabac tin or pyoverdin respectively, were most resistant to Bi3+. Enterochel in or pyochelin producers were less resistant to Bi3+, but more resist ant than strains lacking siderophores. Purified pyoverdin restored Bi3 + resistance in a mutant lacking this siderophore, but not in one lack ing the pyoverdin receptor. Bismuth-treated bacteria exhibited unique outer membrane proteins, similar in size to iron-repressible proteins. Thus, resistance to the inhibitory action of Bi3+ among Gram-negative bacteria is inversely related to iron concentration and strongly depe ndent on iron transport mechanisms. The data suggest that bismuth acti on is largely a nonspecific, competitive interference with iron transp ort, related primarily to atomic valence. Furthermore, resistance to B i3+ among bacteria is predictive of virulence.