Host-induced, stage-specific virulence gene activation in Candida albicans during infection

Peter Staib, Marianne Kretschmar, Thomas Nichterlein, Gerwald Koehler, Sonja Michel, Herbert Hof, Jörg Hacker, Joachim Morschhäuser

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

An understanding of the complex interactions between pathogenic microbes and their host must include the identification of gene expression patterns during infection. To detect the activation of virulence genes in the opportunistic fungal pathogen Candida albicans in vivo by host signals, we devised a reporter system that is based on FLP-mediated genetic recombination. The FLP gene, encoding the site-specific recombinase FLP, was genetically modified for expression in C. albicans and fused to the promoter of the SAP2 gene that codes for one of the secreted aspartic proteinases, which are putative virulence factors of C. albicans. The SAP2P-FLP fusion was integrated into one of the SAP2 alleles in a strain that contained a deletable marker that conferred resistance to mycophenolic acid and was flanked by direct repeats of the FLP recognition target (FRT). Using this reporter system, a transient gene induction could be monitored at the level of single cells by the mycophenolic acid-sensitive phenotype of the colonies generated from such cells after FLP-mediated marker excision. In two mouse models of disseminated candidiasis, SAP2 expression was not observed in the initial phase of infection, but the SAP2 gene was strongly induced after dissemination into deep organs. In contrast, in a mouse model of oesophageal candidiasis in which dissemination into internal organs did not occur, no SAP2 expression was detected at any time. Our results support a role of the SAP2 gene in the late stages of an infection, after fungal spread into deep tissue. This new in vivo expression technology (IVET) for a human fungal pathogen allows the detection of virulence gene induction at different stages of an infection, and therefore provides clues about the role of these genes in the disease process.

Original languageEnglish
Pages (from-to)533-546
Number of pages14
JournalMolecular Microbiology
Volume32
Issue number3
DOIs
StatePublished - 29 May 1999

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Candida albicans
Transcriptional Activation
Virulence
Infection
Genes
Mycophenolic Acid
Candidiasis
Aspartic Acid Proteases
Mycoses
Nucleic Acid Repetitive Sequences
Virulence Factors
Genetic Recombination
Alleles
Technology
Phenotype
Gene Expression

Cite this

Staib, Peter ; Kretschmar, Marianne ; Nichterlein, Thomas ; Koehler, Gerwald ; Michel, Sonja ; Hof, Herbert ; Hacker, Jörg ; Morschhäuser, Joachim. / Host-induced, stage-specific virulence gene activation in Candida albicans during infection. In: Molecular Microbiology. 1999 ; Vol. 32, No. 3. pp. 533-546.
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Staib, P, Kretschmar, M, Nichterlein, T, Koehler, G, Michel, S, Hof, H, Hacker, J & Morschhäuser, J 1999, 'Host-induced, stage-specific virulence gene activation in Candida albicans during infection', Molecular Microbiology, vol. 32, no. 3, pp. 533-546. https://doi.org/10.1046/j.1365-2958.1999.01367.x

Host-induced, stage-specific virulence gene activation in Candida albicans during infection. / Staib, Peter; Kretschmar, Marianne; Nichterlein, Thomas; Koehler, Gerwald; Michel, Sonja; Hof, Herbert; Hacker, Jörg; Morschhäuser, Joachim.

In: Molecular Microbiology, Vol. 32, No. 3, 29.05.1999, p. 533-546.

Research output: Contribution to journalArticle

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