Genes involved in biofilm formation by the pathogenic yeast...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/31 (2006.01) C07K 14/40 (2006.01) C12N 1/16 (2006.01) C12Q 1/68 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2438753

Like many bacteria, yeast species can form biofilms on several surfaces. The properties and way of life in these communities are distinct from those of free-swimming populations. Candida albicans colonizes the surfaces of catheters, prostheses and epithelia, developing biofilms that are extremely resistant to antifungal drugs. Here, we show that different biofilm populations of C. albicans display very similar transcript profiles. Biofilm and planktonic cultures produced under different conditions of nutrient flow, aerobiosis or carbon-source concentration were compared by overall gene-expression correlation. Correlation was much higher between biofilms than planktonic populations irrespective of growth conditions. A cluster of 325 differentially expressed genes was identified. In agreement with the over-representation of amino acid biosynthetic pathways in this cluster, Gcn4p, a regulator of amino acid starvation responses, is required for normal biofilm growth. In an effort to identify biofilm-related genes that are independent of mycelial development, we studied the transcriptome of hyphae switched and un-switched biofilms produced by wild-type and cph1/cph1 efg1/efg1 strains, respectively. Biofilm versus planktonic comparisons in both strains yielded a set of 442 differentially expressed genes, of which 317 were expressed independently of hyphae formation. This subset reveals activation of the sulfur-amino acid biosynthesis pathway as a biofilm-related feature. Our work shows not only that expression of some cell attributes, e.g. amino acid metabolism, change during biofilm growth, but also that the overall transcriptome moves to characteristic expression values. Together, the data suggest transcriptome invariance in different environments as a salient property of C. albicans biofilm populations.

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