2022
DOI: 10.1101/2022.05.25.493415
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Ferric reductase-related proteins mediate fungal heme acquisition

Abstract: Heme can serve as iron source in many environments, including the iron-poor animal host environment. The fungal pathobiont Candida albicans expresses a family of extracellular CFEM hemophores that capture heme from host proteins and transfer it across the cell wall to the cell membrane, to be endocytosed and utilized as heme or iron source. Here we identified Frp1 and Frp2, two ferric reductase (FRE)-related proteins that lack an extracellular N-terminal substrate-binding domain, as being required for hemoglob… Show more

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Cited by 2 publications
(11 citation statements)
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“…Seven other genes occurred once, including FRP2 . FRP2 is the gene most strongly selected for by GaPPIX, however FRP2 mutants are generally not defective in heme uptake in regular YPD medium [22]. A single insertion, near the 3’ end of the coding region, was an exception, for unknown reasons.…”
Section: Resultsmentioning
confidence: 99%
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“…Seven other genes occurred once, including FRP2 . FRP2 is the gene most strongly selected for by GaPPIX, however FRP2 mutants are generally not defective in heme uptake in regular YPD medium [22]. A single insertion, near the 3’ end of the coding region, was an exception, for unknown reasons.…”
Section: Resultsmentioning
confidence: 99%
“…When we tested the induction of heme uptake genes in iron limited medium in the huf1 -/- mutant, we found that absence of Huf1 somewhat reduced the amplitude of induction of RBT5, PGA7 and FRP1 , but strongly reduced the induction of FRP2 . The effect on FRP2 explains why HUF1 was identified in a screen for resistance to GaPPIX, since FRP2 is essential for full GaPPIX toxicity [22]. However FRP2 plays a minor role at best in heme-iron utilization in standard medium [22].…”
Section: Discussionmentioning
confidence: 99%
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“…The observation that these three proteins can all extract heme from hemoglobin and transfer it from one protein to the next [ 18 , 19 ] is consistent with a heme transfer cascade across the cell envelope, followed by internalization via endocytosis [ 11 , 17 ]. Recently, two ferric reductase-like proteins, Frp1 and Frp2, also were identified as necessary for heme utilization and for sensitivity to toxic heme analogs [ 22 ].…”
Section: Introductionmentioning
confidence: 99%