Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Siroheme, the cofactor for sulfite and nitrite reductases, is formed by methylation, oxidation, and iron insertion into the tetrapyrrole uroporphyrinogen III (Uro-III). The CysG protein performs all three steps of siroheme biosynthesis in the enteric bacteria Escherichia coli and Salmonella enterica. In either taxon, cysG mutants cannot reduce sulfite to sulfide and require a source of sulfide or cysteine for growth. In addition, CysG-mediated methylation of Uro-III is required for de novo synthesis of cobalamin (coenzyme B(12)) in S. enterica. We have determined that cysG mutants of the related enteric bacterium Klebsiella aerogenes have no defect in the reduction of sulfite to sulfide. These data suggest that an alternative enzyme allows for siroheme biosynthesis in CysG-deficient strains of Klebsiella. However, Klebsiella cysG mutants fail to synthesize coenzyme B(12), suggesting that the alternative siroheme biosynthetic pathway proceeds by a different route. Gene cysF, encoding an alternative siroheme synthase homologous to CysG, has been identified by genetic analysis and lies within the cysFDNC operon; the cysF gene is absent from the E. coli and S. enterica genomes. While CysG is coregulated with the siroheme-dependent nitrite reductase, the cysF gene is regulated by sulfur starvation. Models for alternative regulation of the CysF and CysG siroheme synthases in Klebsiella and for the loss of the cysF gene from the ancestor of E. coli and S. enterica are presented.
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PMID:Alternative pathways for siroheme synthesis in Klebsiella aerogenes. 1111 33

Staphylococcus aureus SirA was previously identified as a lipoprotein, and SirB and SirC are thought to encode the transmembrane domains of an ABC transporter. Sir proteins show similarity to iron-siderophore transporters in several bacteria. Here, we show that the iron-regulated sirABC operon is divergently transcribed from the sbn operon that encodes enzymes involved in the synthesis of staphylobactin, a recently described siderophore produced by S. aureus. Mutation of either sirA or sirB increased the resistance of iron-starved S. aureus to streptonigrin and resulted in compromised growth in iron-restricted, but not iron-rich, media. We also demonstrated that sirA and sirB mutants are compromised in the ability to transport iron complexed to staphylobactin but are not compromised for uptake of other iron complexes, such as ferric hydroxamates, ferric enterobactin, or ferric citrate. SirA- and SirB-deficient S. aureus, however, retain the ability to produce staphylobactin. Moreover, we found that transcription from the sbn operon was increased, relative to the wild type, in both sirA and sirB knockout strains, likely in response to an increased level of iron starvation in these cells. These results provide evidence of a role for these proteins in iron import in S. aureus and for full fitness of the bacterium in iron-restricted environments and demonstrate a function for S. aureus genes encoding proteins involved in the transport of an endogenously produced siderophore.
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PMID:Involvement of SirABC in iron-siderophore import in Staphylococcus aureus. 1557 85