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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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Comparison of the renal C. albicans SC5314 transcriptome with other in vivo microarray studies. The numbers of genes displaying >2-fold regulation in each study are illustrated in the Venn diagrams. (A) This rabbit renal study compared with the mouse kidney study of Andes and co-workers (2005). (B) This rabbit renal study compared with the mouse intraperitoneal study of Thewes et al. (2007) and the human oral candidiasis study of Zakikhany et al. (2007).
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fig2: Comparison of the renal C. albicans SC5314 transcriptome with other in vivo microarray studies. The numbers of genes displaying >2-fold regulation in each study are illustrated in the Venn diagrams. (A) This rabbit renal study compared with the mouse kidney study of Andes and co-workers (2005). (B) This rabbit renal study compared with the mouse intraperitoneal study of Thewes et al. (2007) and the human oral candidiasis study of Zakikhany et al. (2007).

Mentions: We compared our microarray data on rabbit renal infections with those from two other laboratories that have examined the in vivo transcriptome of C. albicans. Andes and co-workers (2005) examined the C. albicans transcriptome during mouse kidney infections, using YPD-grown cells as their comparator. They reported that 19% of all genes displayed >2-fold regulation in renal tissue compared with YPD-grown controls. They also observed up-regulation of glyoxylate cycle, lipid metabolism and stress genes, and the down regulation of genes involved in translation. However, there is limited overlap between their data and ours with respect to the C. albicans genes that were up- or down-regulated during renal infection (Fig. 2A). This is probably due in part to the different control conditions used in these studies: exponential RPMI 1640-grown cells in our case versus YPD-grown cells in the mouse renal study (Andes et al., 2005). Also, different microarray formats were used: Eurogentec microarrays were used in our case, whereas arrays from the Biotechnology Research Institute, National Research Council, Montreal were used by Andes and co-workers. Finally of course, different mammalian models were used: rabbits versus mice. These parameters might explain why only two C. albicans genes were up-regulated in both datasets: ADR1 and ZRT2, both of which are putative zinc finger transcription factors. ZRT2 is also transcriptionally induced during interactions with macrophages (Lorenz et al., 2004), but down-regulated in vitro in response to heat shock, osmotic stress, oxidative stress and amino acid starvation (Enjalbert et al., 2003; Tournu et al, 2005). Minimal regulation of ADR1 has been reported in transcript profiling studies of in vitro culture conditions.


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)

Comparison of the renal C. albicans SC5314 transcriptome with other in vivo microarray studies. The numbers of genes displaying >2-fold regulation in each study are illustrated in the Venn diagrams. (A) This rabbit renal study compared with the mouse kidney study of Andes and co-workers (2005). (B) This rabbit renal study compared with the mouse intraperitoneal study of Thewes et al. (2007) and the human oral candidiasis study of Zakikhany et al. (2007).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698078&req=5

fig2: Comparison of the renal C. albicans SC5314 transcriptome with other in vivo microarray studies. The numbers of genes displaying >2-fold regulation in each study are illustrated in the Venn diagrams. (A) This rabbit renal study compared with the mouse kidney study of Andes and co-workers (2005). (B) This rabbit renal study compared with the mouse intraperitoneal study of Thewes et al. (2007) and the human oral candidiasis study of Zakikhany et al. (2007).
Mentions: We compared our microarray data on rabbit renal infections with those from two other laboratories that have examined the in vivo transcriptome of C. albicans. Andes and co-workers (2005) examined the C. albicans transcriptome during mouse kidney infections, using YPD-grown cells as their comparator. They reported that 19% of all genes displayed >2-fold regulation in renal tissue compared with YPD-grown controls. They also observed up-regulation of glyoxylate cycle, lipid metabolism and stress genes, and the down regulation of genes involved in translation. However, there is limited overlap between their data and ours with respect to the C. albicans genes that were up- or down-regulated during renal infection (Fig. 2A). This is probably due in part to the different control conditions used in these studies: exponential RPMI 1640-grown cells in our case versus YPD-grown cells in the mouse renal study (Andes et al., 2005). Also, different microarray formats were used: Eurogentec microarrays were used in our case, whereas arrays from the Biotechnology Research Institute, National Research Council, Montreal were used by Andes and co-workers. Finally of course, different mammalian models were used: rabbits versus mice. These parameters might explain why only two C. albicans genes were up-regulated in both datasets: ADR1 and ZRT2, both of which are putative zinc finger transcription factors. ZRT2 is also transcriptionally induced during interactions with macrophages (Lorenz et al., 2004), but down-regulated in vitro in response to heat shock, osmotic stress, oxidative stress and amino acid starvation (Enjalbert et al., 2003; Tournu et al, 2005). Minimal regulation of ADR1 has been reported in transcript profiling studies of in vitro culture conditions.

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