Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae.
The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococcal mutants. Streptonigrin (0.025 microgram/ml) efficiently killed gonococcal strain FA1090, and this effect depended on iron. Streptonigrin-resistant mutant FA6271 had normal iron uptake but was moderately deficient in total iron. Resistance most likely resulted from failure of FA6271 to divert electrons to streptonigrin, as demonstrated by a reduction in KCN-insensitive respiration (a hallmark of the action of quinones) and superoxide formation. Other mutants selected for inability to use human iron-binding proteins (strains FA6273 and FA6275) had no increase in streptonigrin MIC and no decrease in KCN-insensitive respiration. Mutants did not demonstrate an increase in superoxide dismutase or catalase. Streptonigrin killing of gonococci depended on a reaction(s) in which extracellular iron was important, presumably because iron was required for catalysis of hydroxyl radical. The results suggest that a membrane component may be a target for the actions of streptonigrin.
Cohen
M S
MS
Department of Medicine, University of North Carolina, Chapel Hill 27514.
Chai
Y
Y
Britigan
B E
BE
McKenna
W
W
Adams
J
J
Svendsen
T
T
Bean
K
K
Hassett
D J
DJ
Sparling
P F
PF
D002374:Catalase / Q000378:metabolism; D004352:Drug Resistance, Microbial; D005609:Free Radicals; D007202:Indicators and Reagents; D007501:Iron / Q000378:metabolism*; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics; D010101:Oxygen Consumption / Q000187:drug effects; D013308:Streptonigrin / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D007202:Indicators and Reagents; D013481:Superoxides; D013308:Streptonigrin; D007501:Iron; D002374:Catalase