Fur regulation of Staphylococcus aureus heme oxygenases is required for heme homeostasis.

Lojek LJ, Farrand AJ, Weiss A, Skaar EP
Int J Med Microbiol. 2018 308 (6): 582-589

PMID: 29409696 · PMCID: PMC6070430 · DOI:10.1016/j.ijmm.2018.01.009

Heme is a cofactor that is essential for cellular respiration and for the function of many enzymes. If heme levels become too low within the cell, S. aureus switches from producing energy via respiration to producing energy by fermentation. S. aureus encodes two heme oxygenases, IsdI and IsdG, which cleave the porphyrin heme ring releasing iron for use as a nutrient source. Both isdI and isdG are only expressed under low iron conditions and are regulated by the canonical Ferric Uptake Regulator (Fur). Here we demonstrate that unregulated expression of isdI and isdG within S. aureus leads to reduced growth under low iron conditions. Additionally, the constitutive expression of these enzymes leads to decreased heme abundance in S. aureus, an increase in the fermentation product lactate, and increased resistance to gentamicin. This work demonstrates that S. aureus has developed tuning mechanisms, such as Fur regulation, to ensure that the cell has sufficient quantities of heme for efficient ATP production through aerobic respiration.

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MeSH Terms (11)

Aerobiosis Bacterial Proteins Gene Expression Regulation, Bacterial Heme Heme Oxygenase (Decyclizing) Homeostasis Iron Mixed Function Oxygenases Oxygenases Repressor Proteins Staphylococcus aureus

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