1887

Abstract

High-affinity iron uptake by a ferrous permease in the opportunistic pathogen is required for virulence. Here this iron uptake system has been characterized by investigating three distinct activities: an externally directed surface ferric reductase, a membrane-associated PPD (-phenylenediamine) oxidase and a cellular ferrous iron transport activity. Copper was required for the PPD oxidase and ferrous transport activities. In contrast, copper was not required for iron uptake from siderophores. Addition of iron to the growth medium repressed ferric reductase and ferrous transport, indicating homeostatic regulation. To identify the genes involved, orthologous mutants of were transformed with a genomic library of . , a gene with sequence similarity to ferric reductases, restored reductase activity to the orthologous mutant. and , genes with homology to ferrous permeases, conferred ferrous transport activity to the orthologous mutant. However, neither a genomic library nor , a multicopper oxidase homologue and candidate gene for the PPD oxidase, complemented the mutant, possibly because of problems with targeting or assembly. Transcripts for , and were strongly repressed by iron, whereas the transcript was induced by iron. Deletion of the regulator perturbed the homeostatic control of reductive iron uptake. Incidentally, iron starvation was noted to induce flavin production and this was misregulated in the absence of control. The opposite regulation of two iron permease genes and the role of indicate that the process of iron acquisition by may be more complex and potentially more adaptable than by

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2002-01-01
2019-11-14
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