In vitro reconstructed human epithelia reveal contributions of Candida albicans EFG1 and CPH1 to adhesion and invasion

Abstract

The individual and synergistic contributions of two transcription factors, EFG1 and CPH1, have been characterized with regard to adhesion to, and invasion of, human epithelia by Candida albicans. For this purpose two in vitro reconstructed tissue models were developed. A multi-layered model of human epidermis was used to simulate superficial infections of the skin, whereas a reconstructed human intestinal model was used to mimic the first steps of systemic infections. It was shown that C. albicans deleted for both transcription factors CPH1 and EFG1, in contrast to the congenic clinical isolate Sc5314, was neither able to adhere to, nor to penetrate, either of the model systems. A strain deleted for EFG1 alone showed significant reduction in adhesion and was not able to penetrate through the stratum corneum. However, strains deleted for CPH1 showed phenotypes paralleling the phenotypes of the clinical isolate Sc5314. Using different types of multilayered human tissues reconstructed in vitro the individual contributions of Efg1p and Cph1p to two important virulence factors of C. albicans, namely adhesion and invasion, could be defined.

Non-Lethal Candida Albicans CPH1/CPH1 EFG1/EFG1 Transcription Factor Mutant Establishing Restricted Zone of Infection in a Mouse Model of Systemic Infection

“…In addition to filamentous growth, the Cphlp and Efg IP transcription factors also regulate genes such as INTI, HWP1, and other hypha I specific molecules, which may be involved in the process of virulence such as the adhesion of the hyphal cells (12)(13)(14)(15)(16). This is consistent with the observation that the adhesion ability of the cphl/cphl efgJ/efgl mutant cells is less than that of the wild-type cells (12,14). The reduced invasion ability in the mutant cells can be explained by the fact that several aspartic proteinases are also regulated by Efg 1P (17)(18).…”

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.…”

The Activity of Fungichromin against the Formation of <i>Candida albicans</i> Biofilm

“…41) EFG1 and CPH1 genes, as transcriptional regulators, have been identified as having key roles in controlling the growth of hyphae. 42,43) The positive correlation between biofilm formation capacity and genes (ALS1, ALS3, HWP1, HYR1, EFG1, CPH1 and BCR1) has been found. The expression level of the genes (ALS1, ALS3, HWP1, HYR1, EFG1, CPH1 and BCR1) from biofilm is significantly higher than that from planktonic cells.…”