title: Resistance to bismuth among gram-negative bacteria is dependent upon iron and its uptake.
abstract: Bismuth antimicrobial action is poorly understood. Many trivalent metals possess antibacterial activity, especially under low iron conditions. 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 microM Bi3+. Resistance to bismuth action also depended on the production of virulence-related siderophores. Escherichia coli, Aeromonas hydrophila or Pseudomonas aeruginosa producing aerobactin, amonabactin or pyoverdin respectively, were most resistant to Bi3+. Enterochelin or pyochelin producers were less resistant to Bi3+, but more resistant than strains lacking siderophores. Purified pyoverdin restored Bi3+ resistance in a mutant lacking this siderophore, but not in one lacking 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 dependent on iron transport mechanisms. The data suggest that bismuth action is largely a nonspecific, competitive interference with iron-transport, related primarily to atomic valence Furthermore, resistance to Bi3+ among bacteria is predictive of virulence.
authors.affiliation: Infectious Disease Division, Winthrop-University Hospital, Mineola, Long Island, New York 11501, USA.
authors.forename: P
authors.initials: P
authors.lastname: Domenico
authors.forename: J
authors.initials: J
authors.lastname: Reich
authors.forename: W
authors.initials: W
authors.lastname: Madonia
authors.forename: B A
authors.initials: BA
authors.lastname: Cunha
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001729:Bismuth / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003470:Culture Media; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D005290:Ferric Compounds; D001729:Bismuth