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Genome-wide analysis of Candida albicans gene expression patterns during infection of the mammalian kidney.

Walker LA, Maccallum DM, Bertram G, Gow NA, Odds FC, Brown AJ - Fungal Genet. Biol. (2008)

Bottom Line: Global analysis of the molecular responses of microbial pathogens to their mammalian hosts represents a major challenge.To date few microarray studies have been performed on Candida albicans cells derived from infected tissues.When we compared the congenic virulent C. albicans strains NGY152 and SC5314, there was minimal overlap between their transcriptomes during kidney infections.

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.

ABSTRACT
Global analysis of the molecular responses of microbial pathogens to their mammalian hosts represents a major challenge. To date few microarray studies have been performed on Candida albicans cells derived from infected tissues. In this study we examined the C. albicans SC5314 transcriptome from renal infections in the rabbit. Genes involved in adhesion, stress adaptation and the assimilation of alternative carbon sources were up-regulated in these cells compared with control cells grown in RPMI 1640, whereas genes involved in morphogenesis, fermentation and translation were down-regulated. When we compared the congenic virulent C. albicans strains NGY152 and SC5314, there was minimal overlap between their transcriptomes during kidney infections. This suggests that much of the gene regulation observed during infections is not essential for virulence. Indeed, we observed a poor correlation between the transcriptome and phenome for those genes that were regulated during kidney infection and that have been virulence tested.

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Histological analyses indicate that C. albicans SC5314 and NGY152 generate equivalent sizes of lesions and display similar cell morphologies in rabbit renal infections. Scale bars = 50 μm. (A) Low magnification. (B) Higher magnification.
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fig3: Histological analyses indicate that C. albicans SC5314 and NGY152 generate equivalent sizes of lesions and display similar cell morphologies in rabbit renal infections. Scale bars = 50 μm. (A) Low magnification. (B) Higher magnification.

Mentions: The above data suggest that C. albicans genes associated with some virulence factors, fitness attributes and other functions are regulated during infection. We tested this further by examining a second C. albicans strain in the rabbit renal model. We chose the strain NGY152 because this strain is a virulent, prototrophic, congenic derivative of SC5314 (MacCallum and Odds, 2005). We confirmed the comparable virulence levels of these strains in the rabbit model by measuring fungal burdens in both kidneys of infected animals after 72 h of infection. For SC5314, the kidney burdens from one rabbit were 4.0 × 106 and 4.6 × 106 cfu/g, and for a second rabbit were 1.2 × 106 and 1.5 × 106 cfu/g. For NGY152, the kidney burdens in the first rabbit were 4.4 × 106 and 3.7 × 106 cfu/g, and in the second were 2.3 × 106 and 3.8 × 106 cfu/g. Animals infected with both strains displayed signs of clinical deterioration after three days. Furthermore histological analyses confirmed that kidney lesions generated by SC5314 and NGY152 were of similar size, and that SC5314 and NGY152 cells infecting the kidney displayed similar morphologies (Fig. 3). Therefore, the gross pathological effects of both strains were similar.


Genome-wide analysis of Candida albicans gene expression patterns during infection of the mammalian kidney.

Walker LA, Maccallum DM, Bertram G, Gow NA, Odds FC, Brown AJ - Fungal Genet. Biol. (2008)

Histological analyses indicate that C. albicans SC5314 and NGY152 generate equivalent sizes of lesions and display similar cell morphologies in rabbit renal infections. Scale bars = 50 μm. (A) Low magnification. (B) Higher magnification.
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Related In: Results  -  Collection

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fig3: Histological analyses indicate that C. albicans SC5314 and NGY152 generate equivalent sizes of lesions and display similar cell morphologies in rabbit renal infections. Scale bars = 50 μm. (A) Low magnification. (B) Higher magnification.
Mentions: The above data suggest that C. albicans genes associated with some virulence factors, fitness attributes and other functions are regulated during infection. We tested this further by examining a second C. albicans strain in the rabbit renal model. We chose the strain NGY152 because this strain is a virulent, prototrophic, congenic derivative of SC5314 (MacCallum and Odds, 2005). We confirmed the comparable virulence levels of these strains in the rabbit model by measuring fungal burdens in both kidneys of infected animals after 72 h of infection. For SC5314, the kidney burdens from one rabbit were 4.0 × 106 and 4.6 × 106 cfu/g, and for a second rabbit were 1.2 × 106 and 1.5 × 106 cfu/g. For NGY152, the kidney burdens in the first rabbit were 4.4 × 106 and 3.7 × 106 cfu/g, and in the second were 2.3 × 106 and 3.8 × 106 cfu/g. Animals infected with both strains displayed signs of clinical deterioration after three days. Furthermore histological analyses confirmed that kidney lesions generated by SC5314 and NGY152 were of similar size, and that SC5314 and NGY152 cells infecting the kidney displayed similar morphologies (Fig. 3). Therefore, the gross pathological effects of both strains were similar.

Bottom Line: Global analysis of the molecular responses of microbial pathogens to their mammalian hosts represents a major challenge.To date few microarray studies have been performed on Candida albicans cells derived from infected tissues.When we compared the congenic virulent C. albicans strains NGY152 and SC5314, there was minimal overlap between their transcriptomes during kidney infections.

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.

ABSTRACT
Global analysis of the molecular responses of microbial pathogens to their mammalian hosts represents a major challenge. To date few microarray studies have been performed on Candida albicans cells derived from infected tissues. In this study we examined the C. albicans SC5314 transcriptome from renal infections in the rabbit. Genes involved in adhesion, stress adaptation and the assimilation of alternative carbon sources were up-regulated in these cells compared with control cells grown in RPMI 1640, whereas genes involved in morphogenesis, fermentation and translation were down-regulated. When we compared the congenic virulent C. albicans strains NGY152 and SC5314, there was minimal overlap between their transcriptomes during kidney infections. This suggests that much of the gene regulation observed during infections is not essential for virulence. Indeed, we observed a poor correlation between the transcriptome and phenome for those genes that were regulated during kidney infection and that have been virulence tested.

Show MeSH
Related in: MedlinePlus