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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, Warren, Martin J., Prieto, Manuel, Coutinho, Ana, Sousa, Filipa L., Fernandes, Fábio, Saraiva, Lígia M. and others. (2018) Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG. Molecular Microbiology, 109 (3). pp. 385-400. ISSN 0950-382X. (doi:10.1111/mmi.14060) (KAR id:68840)

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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.

Item Type: Article
DOI/Identification number: 10.1111/mmi.14060
Uncontrolled keywords: haem biosynthesis, ferrochelatase, S. aureus, haem uptake, haem monooxygenase
Subjects: H Social Sciences
Divisions: Faculties > Sciences > School of Biosciences
Faculties > Social Sciences > Kent Business School
Depositing User: Martin Warren
Date Deposited: 28 Aug 2018 15:48 UTC
Last Modified: 23 Jan 2020 04:15 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/68840 (The current URI for this page, for reference purposes)
Warren, Martin J.: https://orcid.org/0000-0002-6028-6456
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