Abstract

Geotrichum candidum is capable of utilizing iron from hydroxamate siderophores of different structural classes. The relative rates of iron transport for ferrichrome, ferrichrysin, ferrioxamine B, fusigen, ferrichrome A, rhodotorulic acid, coprogen B, dimerium acid and ferrirhodin were 100%, 98%, 74%, 59%, 49%, 35%, 24%, 12% and 11% respectively. Ferrichrome, ferrichrysine and ferrichrome A inhibited [59Fe]ferrioxamine-B-mediated iron transport by 71%, 68% and 28% respectively when added at equimolar concentrations to the radioactive complex. The inhibitory mechanism of [59Fe]ferrioxamine B uptake by ferrichrome was noncompetitive (Ki 2.4 microM), suggesting that the two siderophores do not share a common transport system. Uptake of [59Fe]ferrichrome, [59Fe]rhodotorulic acid and [59Fe]fusigen was unaffected by competition with the other two siderophores or with ferrioxamine B. Thus, G. candidum may possess independent transport systems for siderophores of different structural classes. The uptake rates of [14C]ferrioxamine B and 67Ga-desferrioxamine B were 30% and 60% respectively, as compared to [59Fe]ferrioxamine B. The specific ferrous chelates, dipyridyl and ferrozine at 6 mM, caused 65% and 35% inhibition of [59Fe]ferrioxamine uptake. From these results we conclude that, although about 70% of the iron is apparently removed from the complex by reduction prior to being transported across the cellular membrane, a significant portion of the chelated ligand may enter the cell intact. The former and latter mechanisms seem not to be mutually exclusive.

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