Participation of Candida albicans Transcription Factor RLM1 in Cell Wall Biogenesis and Virulence

Abstract

Candida albicans cell wall is important for growth and interaction with the environment. RLM1 is one of the putative transcription factors involved in the cell wall integrity pathway, which plays an important role in the maintenance of the cell wall integrity. In this work we investigated the involvement of RLM1 in the cell wall biogenesis and in virulence. Newly constructed C. albicans Δ/Δrlm1 mutants showed typical cell wall weakening phenotypes, such as hypersensitivity to Congo Red, Calcofluor White, and caspofungin (phenotype reverted in the presence of sorbitol), confirming the involvement of RLM1 in the cell wall integrity. Additionally, the cell wall of C. albicans Δ/Δrlm1 showed a significant increase in chitin (213%) and reduction in mannans (60%), in comparison with the wild-type, results that are consistent with cell wall remodelling. Microarray analysis in the absence of any stress showed that deletion of RLM1 in C. albicans significantly down-regulated genes involved in carbohydrate catabolism such as DAK2, GLK4, NHT1 and TPS1, up-regulated genes involved in the utilization of alternative carbon sources, like AGP2, SOU1, SAP6, CIT1 or GAL4, and genes involved in cell adhesion like ECE1, ALS1, ALS3, HWP1 or RBT1. In agreement with the microarray results adhesion assays showed an increased amount of adhering cells and total biomass in the mutant strain, in comparison with the wild-type. C. albicans mutant Δ/Δrlm1 strain was also found to be less virulent than the wild-type and complemented strains in the murine model of disseminated candidiasis. Overall, we showed that in the absence of RLM1 the modifications in the cell wall composition alter yeast interaction with the environment, with consequences in adhesion ability and virulence. The gene expression findings suggest that this gene participates in the cell wall biogenesis, with the mutant rearranging its metabolic pathways to allow the use of alternative carbon sources.

Polymicrobial Ventilator-Associated Pneumonia: Fighting In Vitro Candida albicans-Pseudomonas aeruginosa Biofilms with Antifungal-Antibacterial Combination Therapy

“…Here, it was observed that the C . albicans strain used in this study could produce hyphae under unstressed and stressed situations, as previously demonstrated [114] which could contribute to its high resilience towards antimicrobial treatment and posterior consecutive recoveries of its regrowth aptitude.…”

Critical role for CaFEN1 and CaFEN12 of Candida albicans in cell wall integrity and biofilm formation

“…1). Next, we tested the sensitivity of these deletants to SDS, a detergent usually employed to determine the compactness of the cell wall, since less compact cell wall would allow SDS to readily reach and damage the plasma membrane resulting in cell death945. Scsur4 Δ/Δ strain was found to be SDS-sensitive (Fig.…”

“…Among antifungals that target cell wall, echinocandins and nikkomycin inhibit β-Glucan synthesis and chitin synthesis, respectively. Defective cell wall biogenesis is known to attenuate infections by C. albicans 910. Thus, a better understanding of cell wall biogenesis and integrity may reveal novel targets for antifungal drug development.…”

Regulation of Neurospora crassa cell wall remodeling via the cot-1 pathway is mediated by gul-1

“…In S. cerevisiae and C. albicans, RLM1 has been shown to play key roles in CWI (Dodou and Treisman 1997;Watanabe et al 1997;Delgado-Silva et al 2014). In filamentous fungi, information concerning the involvement of rlm-1 in cell wall remodeling is less clear and in some cases even contradicting (Damveld et al 2005;Fujioka et al 2007, Kovacs et al 2013.…”

“…In various other fungi, Rlm1 has been shown to be involved in the regulation of expression of some cell wall-related biosynthetic enzymes (Damveld et al 2005;Kovacs et al 2013;Levin 2011;Delgado-Silva et al 2014), yet the involvement of Rlm1p homologs in the CWI pathway in filamentous fungi is by far less clear than that established in S. cerevisiae.…”