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Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization
Ziva Weissman1, Daniel Kornitzer
1Department of Molecular Microbiology, Technion - B. Rappaport Faculty of Medicine, and the Rappaport Institute for Research in the Medical Sciences, Haifa 31096, Israel.
Abstract:
The ability to acquire iron from host tissues is a major virulence factor of pathogenic microorganisms. Candida albicans is an important fungal pathogen, responsible for an increasing proportion of systemic infections. C. albicans, like many pathogenic bacteria, is able to utilize haemin and haemoglobin as iron sources. However, the molecular basis of this pathway in pathogenic fungi is unknown. Here, we identify a conserved family of plasma membrane-anchored proteins as haem-binding proteins that are involved in haem-iron utilization. We isolated RBT51 as a gene that is sufficient by itself to confer to S. cerevisiae the ability to utilize haemoglobin iron. RBT51 is highly homologous to RBT5, which was previously identified as a gene negatively regulated by the transcriptional suppressor CaTup1. Rbt5 and Rbt51 are mannosylated proteins that carry the conserved CFEM domain. We find that RBT5 is strongly induced by starvation for iron, and that deletion of RBT5 is by itself sufficient to significantly reduce the ability of C. albicans to utilize haemin and haemoglobin as iron sources. Iron starvation-inducible, antigenically cross-reacting haem-binding proteins are also present in other Candida species that are able to utilize haem-iron, underscoring the conservation of this iron acquisition pathway among pathogenic fungi.
Insights
Pathogenic fungi like Candida albicans use host iron for virulence. Researchers identified RBT5 and RBT51 proteins crucial for utilizing hemoglobin iron, a key step in fungal infection.
Area of Science:
- Microbiology
- Mycology
- Molecular Biology
Background:
- Iron acquisition is vital for pathogenic microorganisms' virulence.
- Candida albicans is a significant fungal pathogen causing systemic infections.
- The molecular mechanisms of iron utilization from host heme and hemoglobin in fungi remain largely unknown.
Purpose of the Study:
- To identify and characterize the molecular basis of heme-iron utilization in pathogenic fungi.
- To investigate the role of specific proteins in enabling Candida albicans to acquire iron from host sources.
Main Methods:
- Gene isolation and functional analysis in Saccharomyces cerevisiae.
- Homology studies and protein characterization (mannosylation, CFEM domain).
- Gene deletion studies in Candida albicans to assess iron utilization capabilities.
Main Results:
- RBT51 gene confers hemoglobin iron utilization ability to S. cerevisiae.
- RBT5 and RBT51 are homologous, mannosylated, plasma membrane-anchored proteins with a CFEM domain.
- RBT5 deletion significantly impairs C. albicans' ability to utilize heme and hemoglobin for iron.
Conclusions:
- A conserved family of plasma membrane-anchored, heme-binding proteins, including Rbt5 and Rbt51, are involved in fungal heme-iron utilization.
- RBT5 is induced by iron starvation and plays a critical role in C. albicans iron acquisition.
- This iron acquisition pathway is conserved among pathogenic fungi, highlighting its importance in virulence.
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