The three Aspergillus fumigatus CFEM-domain GPI-anchored proteins (CfmA-C) affect cell-wall stability but do not play a role in fungal virulence

Vaknin, Yakir; Shadkchan, Yana; Levdansky, Emma; Morozov, Michael; Romano, Jacob; Osherov, Nir

doi:10.1016/j.fgb.2013.12.005

Cited by 53 publications

(45 citation statements)

References 22 publications

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“…Candida albicans also produces the haemolytic molecule mannan which facilitates access to haembound iron (Tanaka et al, 1997;Watanabe et al, 1999). Interestingly, Aspergillus fumigatus lacks the ability to use haem as an iron source (Eisendle et al, 2003) and its CFEM domain proteins do not play a role in either haem uptake or virulence (Vaknin et al, 2014).…”

Section: Haem Uptake Systemsmentioning

confidence: 99%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

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Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.

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Section: Haem Uptake Systemsmentioning

confidence: 99%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

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“…However, Vaknin et al. found that CFEM‐domain GPI‐anchored proteins affect cell wall stability but do not play a role in fungal virulence of Aspergillus fumigatus , so whether these proteins play a role in Ptt virulence needs confirmation.…”

Section: Resultsmentioning

confidence: 99%

Secretome analysis of virulentPyrenophora teresf. teresisolates

Ismail

Able

2016

Proteomics

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Pyrenophora teres f. teres (Ptt) causes net form net blotch disease of barley, partially by producing necrosis-inducing proteins. The protein profiles of the culture filtrates of 28 virulent isolates were compared by a combination of 2DE and 1D-PAGE with 105 spots and 51 bands chosen for analysis by liquid chromatography electrospray ionization tandem mass spectrometry. A total of 259 individual proteins were identified with 63 of these proteins being common to the selected virulent isolates. Ptt secretes a broad spectrum of proteins including cell wall degrading enzymes; virulence factors and effectors; proteins associated with fungal pathogenesis and development; and proteins related to oxidation-reduction processes. Potential virulence factors and effectors identified included proteins with glucosidase activity, ricin B and concanavalin A-like lectins, glucanases, spherulin, cutinase, pectin lyase, leucine-rich repeat protein, and ceratoplatanin. Small proteins with unknown function but cysteine-rich, common to effectors, were also identified. Differences in the secretion profile of the Ptt isolates have also provided important insight into the different mechanisms contributing to virulence and the development of net form net blotch symptoms.

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“…In contrast, deletion of three genes ( cfmA-C ) encoding CFEM-domain proteins in A. fumigatus did not reveal roles in heme uptake or biofilm formation, although cell wall defects were observed. 86 The lack of an involvement of CfmA-C in heme use is interesting given a recent detailed RNA-Seq analysis indicates that A. fumigatus expresses functions for iron homeostasis, secondary metabolism and detoxification to survive in blood, but does not grow. 87 This has been termed a ‘‘just wait and see’’ resting stage behavior for the fungus.…”

Section: Heme and Hemoglobin Are Important Iron Sources For Pathogmentioning

confidence: 99%

Iron acquisition in fungal pathogens of humans

2017

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The devastating infections that fungal pathogens cause in humans are underappreciated relative to viral, bacterial and parasitic diseases. In recent years, the contributions to virulence of reductive iron uptake, siderophore-mediated uptake and heme acquisition have been identified in the best studied and most life-threatening fungal pathogens: Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. In particular, exciting new work illustrates the importance of iron acquisition from heme and hemoglobin in the virulence of pathogenic yeasts. However, the challenge of establishing how these fungi gain access to hemoglobin in blood and to other sources of heme remains to be fully addressed. Recent studies are also expanding our knowledge of iron uptake in less-well studied fungal pathogens, including dimorphic fungi where new information reveals an integration of iron acquisition with morphogenesis and cell-surface properties for adhesion to host cells. Overall, the accumulating information provides opportunities to exploit iron acquisition for antifungal therapy, and new work highlights the development of specific inhibitors of siderophore biosynthesis and metal chelators for therapeutic use alone or in conjunction with existing antifungal drugs. It is clear that iron-related therapies will need to be customized for specific diseases because the emerging view is that fungal pathogens use different combinations of strategies for iron acquisition in the varied niches of vertebrate hosts.

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The three Aspergillus fumigatus CFEM-domain GPI-anchored proteins (CfmA-C) affect cell-wall stability but do not play a role in fungal virulence

Cited by 53 publications

References 22 publications

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Secretome analysis of virulentPyrenophora teresf. teresisolates

Iron acquisition in fungal pathogens of humans

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