Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG

Marco A.M. Videira, Susana A.L. Lobo, Liliana S.O. Silva, David J. Palmer, Martin J. Warren, Manuel Prieto, Ana Coutinho, Filipa L. Sousa, Fábio Fernandes, Lígia M. Saraiva

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Haem is an essential cofactor in central metabolic pathways in the vast majority of living systems. Prokaryotes acquire haem via haem biosynthesis pathways, and some also utilize haem uptake systems, yet it remains unclear how they balance haem requirements with the paradox that free haem is toxic. Here, using the model pathogen Staphylococcus aureus, we report that IsdG, one of two haem oxygenase enzymes in the haem uptake system, inhibits the formation of haem via the internal haem biosynthesis route. More specifically, we show that IsdG decreases the activity of ferrochelatase and that the two proteins interact both in vitro and in vivo. Further, a bioinformatics analysis reveals that a significant number of haem biosynthesis pathway containing organisms possess an IsdG-homologue and that those with both biosynthesis and uptake systems have at least two haem oxygenases. We conclude that IsdG-like proteins control intracellular haem levels by coupling the two pathways. IsdG is thus a target for the treatment of S. aureusinfections.

Original languageEnglish
Pages (from-to)385-400
Number of pages16
JournalMolecular Microbiology
Volume109
Issue number3
DOIs
Publication statusPublished - 1 Aug 2018

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Mixed Function Oxygenases
Heme
Staphylococcus aureus
Heme Oxygenase (Decyclizing)
Ferrochelatase
Poisons
Metabolic Networks and Pathways
Computational Biology

Cite this

Videira, Marco A.M. ; Lobo, Susana A.L. ; Silva, Liliana S.O. ; Palmer, David J. ; Warren, Martin J. ; Prieto, Manuel ; Coutinho, Ana ; Sousa, Filipa L. ; Fernandes, Fábio ; Saraiva, Lígia M. / Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG. In: Molecular Microbiology. 2018 ; Vol. 109, No. 3. pp. 385-400.
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Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG. / Videira, Marco A.M.; Lobo, Susana A.L.; Silva, Liliana S.O.; Palmer, David J.; Warren, Martin J.; Prieto, Manuel; Coutinho, Ana; Sousa, Filipa L.; Fernandes, Fábio; Saraiva, Lígia M.

In: Molecular Microbiology, Vol. 109, No. 3, 01.08.2018, p. 385-400.

Research output: Contribution to journalArticle

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AU - Lobo, Susana A.L.

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AU - Palmer, David J.

AU - Warren, Martin J.

AU - Prieto, Manuel

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AU - Fernandes, Fábio

AU - Saraiva, Lígia M.

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