A triple mutant lacking the genes yggX, cyaY, and gshA was highly sensitive to low levels of cobalt in minimal medium.  YggX and CyaY are iron-binding proteins that are believed to be involved in iron trafficking.  The gshA gene encodes for a protein involved in the synthesis of the cellular reductant glutathione, the loss of which disrupts iron homeostasis.  It was found that the triple mutant strain required both thiamin and cysteine in order to grow in the presence of cobalt concentrations as low as 10 µM.  Investigation of a wild-type strain indicated that in the presence of 160 µM cobalt, a similar requirement for cysteine could be generated.  Nutritional studies of the cobalt dependent cysteine requirement showed that iron could suppress the cysteine requirement.  Sulfur sources entering the sulfur assimilation pathway after the action of sulfite reductase, but not before, were better at correcting the cobalt dependent defect.  These data led to a model in which cobalt toxicity was caused by a disruption of iron homeostasis leading to a defect in siroheme synthesis, a cofactor required for sulfite reductase function.  This model is supported by data showing other cobalt dependent disruptions of iron homeostasis including the deregulation of Fur regulated genes and a decrease in aconitase activity.  These data provide a platform for studies using cobalt to further probe cellular components involved in iron homeostasis.