A Relay Network of Extracellular Heme-Binding Proteins Drives Iron Acquisition from Hemoglobin


Candida albicans, a commensal fungus of human mucosal surfaces in healthy individuals, is a common cause of superficial infections, as well as of life-threatening systemic infections in individuals suffering from a reduced immune function. As a systemic pathogen, it has to cope with a scarcity of specific nutrients in the host environment, chief among them iron. To overcome this iron limitation, C. albicans is able to extract iron from heme and hemoglobin, the largest iron pools in the human body, via a pathway that involves endocytosis into the cell. Here we show that efficient heme uptake relies on a family of extracellularly-anchored proteins that serve as heme receptors, two of which, at least, are required for efficient heme utilization. Our data suggest the existence of a relay system that transfers heme from one protein to the next across the cell envelope, explaining the requirement for multiple heme receptors for efficient heme-iron utilization. This study extends our understanding of the pathway of host heme utilization by fungal pathogens, and provides new insights into the question of how nutrients such as heme cross the fungal cell wall.


Vyšlo v časopise: A Relay Network of Extracellular Heme-Binding Proteins Drives Iron Acquisition from Hemoglobin. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004407
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004407

Souhrn

Candida albicans, a commensal fungus of human mucosal surfaces in healthy individuals, is a common cause of superficial infections, as well as of life-threatening systemic infections in individuals suffering from a reduced immune function. As a systemic pathogen, it has to cope with a scarcity of specific nutrients in the host environment, chief among them iron. To overcome this iron limitation, C. albicans is able to extract iron from heme and hemoglobin, the largest iron pools in the human body, via a pathway that involves endocytosis into the cell. Here we show that efficient heme uptake relies on a family of extracellularly-anchored proteins that serve as heme receptors, two of which, at least, are required for efficient heme utilization. Our data suggest the existence of a relay system that transfers heme from one protein to the next across the cell envelope, explaining the requirement for multiple heme receptors for efficient heme-iron utilization. This study extends our understanding of the pathway of host heme utilization by fungal pathogens, and provides new insights into the question of how nutrients such as heme cross the fungal cell wall.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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