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Metabolism impacts upon Candida immunogenicity and pathogenicity at multiple levels.

Brown AJ, Brown GD, Netea MG, Gow NA - Trends Microbiol. (2014)

Bottom Line: Metabolism is integral to the pathogenicity of Candida albicans, a major fungal pathogen of humans.As well as providing the platform for nutrient assimilation and growth in diverse host niches, metabolic adaptation affects the susceptibility of C. albicans to host-imposed stresses and antifungal drugs, the expression of key virulence factors, and fungal vulnerability to innate immune defences.Therefore, current concepts of Candida-host interactions must be extended to include the impact of metabolic adaptation upon pathogenicity and immunogenicity.

View Article: PubMed Central - PubMed

Affiliation: Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: al.brown@abdn.ac.uk.

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Nutrients influence the expression of key virulence factors in Candida albicans. Nutrient adaptation influences the expression of secreted aspartic proteases (SAPs), yeast–hypha morphogenesis, adhesion, and biofilm formation via an integrated network of metabolic and virulence signalling pathways. The images of white and opaque cells are from Zordan et al.[61], and the image of C. albicans adhesion is from Delgado-Silva et al.[100]. The SAP crystal structure is reproduced, with permission, from Cutfield et al.[101], and the biofilm images from Nobile et al.[72].
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fig0010: Nutrients influence the expression of key virulence factors in Candida albicans. Nutrient adaptation influences the expression of secreted aspartic proteases (SAPs), yeast–hypha morphogenesis, adhesion, and biofilm formation via an integrated network of metabolic and virulence signalling pathways. The images of white and opaque cells are from Zordan et al.[61], and the image of C. albicans adhesion is from Delgado-Silva et al.[100]. The SAP crystal structure is reproduced, with permission, from Cutfield et al.[101], and the biofilm images from Nobile et al.[72].

Mentions: In addition to enhancing stress resistance and promoting cell wall remodelling, there are longstanding reports showing that metabolic adaptation influences the pathogenicity of C. albicans by modulating the expression of key virulence factors (Figure 2). For example, glucose is one of several stimuli that can trigger hyphal morphogenesis, and glycolytic genes are induced during this yeast-to-hypha transition [49,50]. In addition, metabolic genes account for approximately one-third of genes that are regulated during the white–opaque phenotypic switch: white cells upregulate glycolytic genes whereas opaque cells upregulate genes involved in respiratory metabolism [29]. The expression of secreted aspartic proteinase (SAP) genes is regulated in response to available nitrogen and carbon sources [51]. For example, SAP2 is expressed at high levels during growth on glycerol, at medium levels on glucose or galactose, and at low levels when C. albicans cells are grown on ethanol [51]. Furthermore, growth on different dietary sugars strongly influences the adhesion of C. albicans to abiotic and host surfaces [52,53], and also biofilm formation [54].


Metabolism impacts upon Candida immunogenicity and pathogenicity at multiple levels.

Brown AJ, Brown GD, Netea MG, Gow NA - Trends Microbiol. (2014)

Nutrients influence the expression of key virulence factors in Candida albicans. Nutrient adaptation influences the expression of secreted aspartic proteases (SAPs), yeast–hypha morphogenesis, adhesion, and biofilm formation via an integrated network of metabolic and virulence signalling pathways. The images of white and opaque cells are from Zordan et al.[61], and the image of C. albicans adhesion is from Delgado-Silva et al.[100]. The SAP crystal structure is reproduced, with permission, from Cutfield et al.[101], and the biofilm images from Nobile et al.[72].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4222764&req=5

fig0010: Nutrients influence the expression of key virulence factors in Candida albicans. Nutrient adaptation influences the expression of secreted aspartic proteases (SAPs), yeast–hypha morphogenesis, adhesion, and biofilm formation via an integrated network of metabolic and virulence signalling pathways. The images of white and opaque cells are from Zordan et al.[61], and the image of C. albicans adhesion is from Delgado-Silva et al.[100]. The SAP crystal structure is reproduced, with permission, from Cutfield et al.[101], and the biofilm images from Nobile et al.[72].
Mentions: In addition to enhancing stress resistance and promoting cell wall remodelling, there are longstanding reports showing that metabolic adaptation influences the pathogenicity of C. albicans by modulating the expression of key virulence factors (Figure 2). For example, glucose is one of several stimuli that can trigger hyphal morphogenesis, and glycolytic genes are induced during this yeast-to-hypha transition [49,50]. In addition, metabolic genes account for approximately one-third of genes that are regulated during the white–opaque phenotypic switch: white cells upregulate glycolytic genes whereas opaque cells upregulate genes involved in respiratory metabolism [29]. The expression of secreted aspartic proteinase (SAP) genes is regulated in response to available nitrogen and carbon sources [51]. For example, SAP2 is expressed at high levels during growth on glycerol, at medium levels on glucose or galactose, and at low levels when C. albicans cells are grown on ethanol [51]. Furthermore, growth on different dietary sugars strongly influences the adhesion of C. albicans to abiotic and host surfaces [52,53], and also biofilm formation [54].

Bottom Line: Metabolism is integral to the pathogenicity of Candida albicans, a major fungal pathogen of humans.As well as providing the platform for nutrient assimilation and growth in diverse host niches, metabolic adaptation affects the susceptibility of C. albicans to host-imposed stresses and antifungal drugs, the expression of key virulence factors, and fungal vulnerability to innate immune defences.Therefore, current concepts of Candida-host interactions must be extended to include the impact of metabolic adaptation upon pathogenicity and immunogenicity.

View Article: PubMed Central - PubMed

Affiliation: Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: al.brown@abdn.ac.uk.

Show MeSH
Related in: MedlinePlus