1887

Abstract

Sulfur metabolism has been implicated in the virulence, antibiotic resistance and anti-oxidant defence of . Despite its human disease relevance, sulfur metabolism in mycobacteria has not yet been fully characterized. ATP sulfurylase catalyses the synthesis of activated sulfate (adenosine 5′-phosphosulfate, APS), the first step in the reductive assimilation of sulfate. Expression of the gene, predicted to encode the adenylyl-transferase subunit of ATP sulfurylase, is upregulated by the bacilli inside its preferred host, the macrophage. This study demonstrates that and orthologues exist in and constitute an operon whose expression is induced by sulfur limitation and repressed by the presence of cysteine, a major end-product of sulfur assimilation. The genes are also induced upon exposure to oxidative stress, suggesting regulation of sulfur assimilation by in response to toxic oxidants. To ensure that the operon encoded the activities predicted by its primary sequence, and to begin to characterize the products of the operon, they were expressed in , purified to homogeneity, and tested for their catalytic activities. The CysD and CysNC proteins were shown to form a multifunctional enzyme complex that exhibits the three linked catalytic activities that constitute the sulfate activation pathway.

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2004-06-01
2020-03-30
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