Candida albicans Biofilms: a Developmental State Associated With Specific and Stable Gene Expression Patterns

Abstract

Like many bacteria, yeast species can form biofilms on several surfaces. Candida albicans colonizes the surfaces of catheters, prostheses, and epithelia, forming biofilms that are extremely resistant to antifungal drugs. We have used transcript profiling to investigate the specific properties of C. albicans biofilms. Biofilm and planktonic cultures produced under different conditions of nutrient flow, aerobiosis, or glucose concentration were compared by overall gene expression correlation. Correlation was much higher between biofilms than planktonic populations irrespective of the growth conditions, indicating that biofilm populations formed in different environments display very similar and specific transcript profiles. A first cluster of 325 differentially expressed genes was identified. In agreement with the overrepresentation of amino acid biosynthesis genes in this cluster, Gcn4p, a regulator of amino acid metabolism, was shown to be required for normal biofilm growth. To identify biofilm-related genes that are independent of mycelial development, we studied the transcriptome of biofilms produced by a wild-type, hypha-producing strain and a cph1/cph1 efg1/efg1 strain defective for hypha production. This analysis identified a cluster of 317 genes expressed independently of hypha formation, whereas 86 genes were dependent on mycelial development. Both sets revealed the activation of the sulfur-amino acid biosynthesis pathway as a feature of C. albicans biofilms.

Transcriptional and translational expression patterns associated with immobilized growth of Campylobacter jejuni

“…Many of the membrane proteins that undergo differential expression as a consequence of growth on agar are associated with the primary active transport of amino acids. To our knowledge there have been no previous connections proposed between either low-iron adaptation or biofilm formation and amino acid transport and metabolism, although amino acid starvation was identified as a trigger for biofilm formation for Candida albicans (Garcia-Sanchez et al, 2004). The induction of ABC transport systems which are not specific to amino acid transport has been reported as a consequence of biofilm formation (Pysz et al, 2004) although the functional relevance remains unclear.…”

A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing

“…In the case of fungal biofilms, models used by different groups of investigators include the use of catheter disks, sheets and tubing from a variety of materials normally placed inside some type of sterile receptacle, glass and plastic slides, a perfused biofilm fermentor, microfermentors, cylindrical cellulose filters, acrylic strips and discs, germanium substratum, tissue culture flasks, syringes, modified Robbins devices, the Calgary biofilm device, the CDC reactor, etc., also including both biofilms formed under static and flow-through conditions [10][11][12][13][14][15][16][17][18][19][20][21] . Perhaps with the exception of the Calgary biofilm device, most of these models are complex, technically demanding and generally not amenable to high throughput screening since relatively few equivalent biofilms can be produced at the same time 6 .…”

Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation inCandida albicans

“…However, Efg1 also regulates other genes that are not modulated by the cAMP pathway (Sohn et al, 2003;Doedt et al, 2004;Harcus et al, 2004;Setiadi et al, 2006). Numerous in vitro and in vivo studies with efg1 mutants have demonstrated that Efg1 is important for C. albicans virulence and for the interactions of C. albicans with endothelial and epithelia cells, as well as biofilm formation and catheter infection (Lo et al, 1997;Phan et al, 2000;Dieterich et al, 2002;Lewis et al, 2002;Ramage et al, 2002;Garcia-Sanchez et al, 2004). Despite its importance, molecular mechanisms for how Efg1 regulates gene expression during hyphal development and other processes are still unknown.…”