Candida pathogenesis: Unravelling the threads of infection

Corner, Brian E.; Magee, Patrick

doi:10.1016/s0960-9822(06)00357-5

Cited by 71 publications

(54 citation statements)

References 10 publications

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“…The effects of serum in repressing reductase activity (CaFRE1) while inducing transport of ferrichrome type siderophores (and CaSIT1) indicate that another layer of regulatory complexity exists in C. albicans. Candidate genes for carrying signals for control of the different iron uptake systems include components of the MAP kinase and cAMP signalling pathways that mediate morphologic changes in response to serum (Kobayashi and Cutler, 1998;Corner and Magee, 1997). Another unresolved issue is whether iron or an iron containing protein also act upstream in one of these pathways.…”

Section: Discussionmentioning

confidence: 99%

Siderophore uptake by Candida albicans: effect of serum treatment and comparison with Saccharomyces cerevisiae

Lesuisse

Knight

Camadro

et al. 2002

Yeast

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Iron uptake systems often function as virulence factors in pathogenic organisms. Candida albicans is a fungal pathogen that infects immunocompromised hosts, such as AIDS patients or granulocytopenic bone marrow transplant recipients. Here we show that iron uptake from siderophores occurs in C. albicans and is mediated by one or more highaffinity transport systems. Iron carried on ferrioxamine B, triacethyl-fusarinine, ferrichrome, or ferricrocin was actively taken up via a high-affinity mechanism. The kinetic parameters of uptake were similar to those found in S. cerevisiae. Furthermore, for ferrichrome and ferrioxamine B, cellular uptake of fluorescent analogues was observed. In C. albicans, iron uptake from siderophores was regulated by iron availability, with iron deprivation inducing uptake. Serum exposure, which induces a morphogenic shift from yeast to filamentous forms known to be required for virulence, also resulted in induction of iron transport from ferrichrome-type siderophores. In a tup1/tup1 strain which grows constitutively in the filamentous form, iron transport was derepressed for all siderophores tested. The genes mediating uptake and utilization of iron from siderophores in C. albicans have not been identified; however, the transcript abundance for CaSIT1 was regulated in a manner consistent with the pattern of iron uptake from ferrichrome-type siderophores. Furthermore, CaSIT1 overexpression in S. cerevisiae resulted in inhibited siderophore iron uptake, suggesting that the expressed protein may interact with proteins of S. cerevisiae involved in iron uptake from siderophores. In summary, iron uptake from ferrichrome-type siderophores was induced in filamentous C. albicans, and a potential role of this iron acquisition system in pathogenicity should be considered.

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Section: Discussionmentioning

confidence: 99%

Siderophore uptake by Candida albicans: effect of serum treatment and comparison with Saccharomyces cerevisiae

Lesuisse

Knight

Camadro

et al. 2002

Yeast

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“…The reduced growth rate of crk1/crk1 may contribute to the reduced virulence. The reduced virulence could also be due to the impaired ability of crk1/crk1 strains to undergo hyphal formation, as many mutants defective in hyphal formation have been shown to be less virulent or avirulent compared to the wild type (14,22,35,39). Alternatively, there may be other targets of Crk1 that are not involved in hyphal growth but are required for virulence.…”

Section: Discussionmentioning

confidence: 99%

“…Both growth forms coexist in infected tissues. Because mutant strains defective in morphological switching are much less virulent than wild-type strains (14,22,35,39), competence to perform the switch has been linked with pathogenicity in C. albicans. Hyphal cells have been suggested to aid in adhesion and penetration of epithelial or endothelial cell layers to facilitate the infection (24).…”

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confidence: 99%

Crk1, a Novel Cdc2-Related Protein Kinase, Is Required for Hyphal Development and Virulence in Candida albicans

Chen

Zhou

Wang

et al. 2000

Molecular and Cellular Biology

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Both mitogen-activated protein kinases and cyclin-dependent kinases play a role in hyphal development in Candida albicans. Using an oligonucleotide probe-based screen, we have isolated a new member of the Cdc2 kinase subfamily, designated Crk1 (Cdc2-related kinase). The protein sequence of Crk1 is most similar to those of Saccharomyces cerevisiae Sgv1 and human Pkl1/Cdk9. In S. cerevisiae, CRK1 suppresses some, but not all, of the defects associated with an sgv1 mutant. Deleting both copies of CRK1 in C. albicans slows growth slightly but leads to a profound defect in hyphal development under all conditions examined. crk1/crk1 mutants are impaired in the induction of hypha-specific genes and are avirulent in mice. Consistent with this, ectopic expression of the Crk1 kinase domain (CRK1N) promotes filamentous or invasive growth in S. cerevisiae and hyphal development in C. albicans. The activity of Crk1 in S. cerevisiae requires Flo8 but is independent of Ste12 and Phd1. Similarly, Crk1 promotes filamentation through a route independent of Cph1 and Efg1 in C. albicans. RAS1V13 can also activate filamentation in a cph1/cph1 efg1/efg1 double mutant. Interestingly, CRK1N produces florid hyphae in ras1/ras1 strains, while RAS1 V13 generates feeble hyphae in crk1/crk1 strains.

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“…Dimorphic growth, the ability to grow in more than one form, is believed to contribute to the pathogenicity of C. albicans (Corner and Magee, 1997). Mutant strains that are defective in switching between ®lamentous growth and budding growth frequently exhibit reduced virulence (Sobel et al, 1984;Shepherd, 1985;Ryley and Ryley, 1990;Leberer et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene

Brown

Giusani

Chen

et al. 1999

Molecular Microbiology

250

248

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Hyphal growth in the opportunistic fungal pathogen Candida albicans is believed to contribute to the virulence of the organism by promoting penetration of fungal cells into host tissue. In this study, stimulation of hyphal growth by a feature of the physical environment was demonstrated. Specifically, growth of cells embedded within a matrix promoted the formation of hyphae. The CZF1 gene, encoding a putative transcription factor, was shown to be involved in the regulation of hyphal growth under certain conditions, including embedded conditions. Ectopic expression of CZF1 in embedded cells promoted the rapid formation of hyphae. Elimination of CZF1 and CPH1, encoding a homologue of the Saccharomyces cerevisiae Ste12p transcription factor, led to a pronounced defect in filamentous growth of embedded cells. Elimination of CZF1 alone led to a moderate defect in hyphal growth under some conditions, including embedded conditions. Hyphal morphogenesis in response to matrix embedding may occur in the opportunistic pathogen, C. albicans, to promote invasion of fungal cells into host tissue.

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Candida pathogenesis: Unravelling the threads of infection

Abstract: Recent studies are beginning to delineate those pathways by which the important pathogen Candida albicans switches from one growth form to another; at the same time, insights are being gained into the importance of growth form in pathogenesis.

Cited by 71 publications

References 10 publications

Siderophore uptake by Candida albicans: effect of serum treatment and comparison with Saccharomyces cerevisiae

Siderophore uptake by Candida albicans: effect of serum treatment and comparison with Saccharomyces cerevisiae

Crk1, a Novel Cdc2-Related Protein Kinase, Is Required for Hyphal Development and Virulence in Candida albicans

Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene

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