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

Autor: Videira MAM; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal., Lobo SAL; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.; iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal., Silva LSO; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal., Palmer DJ; School of Biosciences, University of Kent, Giles Lane, Canterbury, UK., Warren MJ; School of Biosciences, University of Kent, Giles Lane, Canterbury, UK., Prieto M; Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal., Coutinho A; Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.; Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal., Sousa FL; Department of Ecogenomics and Systems Biology, University of Vienna, Vienna, Austria., Fernandes F; Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.; Research Unit on Applied Molecular Biosciences-Rede de Química e Tecnologia (UCIBIO-REQUIMTE), Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal., Saraiva LM; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
Jazyk: angličtina
Zdroj: Molecular microbiology [Mol Microbiol] 2018 Aug; Vol. 109 (3), pp. 385-400. Date of Electronic Publication: 2018 Aug 02.
DOI: 10.1111/mmi.14060
Abstrakt: 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.
(© 2018 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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