Candida albicans strains adapted to the mouse gut are resistant to bile salts via a Flo8-dependent mechanism.

Candidaalbicans normally colonizes the human gastrointestinal tract as a commensal. Studying fungal factors involved in colonizing the mammalian gastrointestinal tract requires mouse models with altered microbiota. We have obtained strains of C.

Morphogenetic transitions in the adaptation of Candida albicans to the mammalian gut.

Candida albicans is a pathobiont in humans that forms part of the mycobiota in healthy individuals and can cause different pathologies upon alterations of the host defenses. The mammalian gut is clinically relevant as this niche is the most common pool for bloodstream-derived infections. The ability of C.

Overexpression of the White Opaque Switching Master Regulator Wor1 Alters Lipid Metabolism and Mitochondrial Function in .

is a commensal yeast that inhabits the gastrointestinal tract of humans; increased colonization of this yeast in this niche has implicated the master regulator of the white-opaque transition, Wor1, by mechanisms not completely understood. We have addressed the role that this transcription factor has on commensalism by the characterization of strains overexpressing this gene. We show that overexpression causes an alteration of the total lipid content of the fungal cell and significantly alters the composition of structural and reserve molecular species lipids as determined by lipidomic analysis.

Identification of Clinical Isolates of with Increased Fitness in Colonization of the Murine Gut.

The commensal and opportunistic pathogen is an important cause of fungal diseases in humans, with the gastrointestinal tract being an important reservoir for its infections. The study of the mechanisms promoting the commensal state has attracted considerable attention over the last few years, and several studies have focused on the identification of the intestinal human mycobiota and the characterization of genes involved in its establishment as a commensal. In this work, we have barcoded 114 clinical isolates to identify strains with an enhanced fitness in a murine gastrointestinal commensalism model.

The Glyoxylate Cycle Is Involved in White-Opaque Switching in .

is a commensal yeast that inhabits the gastrointestinal tract of humans. The master regulator of the white-opaque transition has been implicated in the adaptation to this commensal status. A proteomic analysis of cells overexpressing this transcription factor () suggested an altered metabolism of carbon sources and a phenotypic analysis confirmed this alteration.

Cooperative Role of MAPK Pathways in the Interaction of with the Host Epithelium.

is an important human fungal pathogen responsible for tens of millions of infections as well as hundreds of thousands of severe life-threatening infections each year. MAP kinase (MAPK) signal transduction pathways facilitate the sensing and adaptation to external stimuli and control the expression of key virulence factors such as the yeast-to-hypha transition, the biogenesis of the cell wall, and the interaction with the host. In the present study, we have combined molecular approaches and infection biology to analyse the role of MAPK pathways during an epithelial invasion.

The MAPK Hog1 mediates the response to amphotericin B in Candida albicans.

The HOG MAP kinase pathway plays a crucial role in the response to different stresses in the opportunistic pathogen Candida albicans. The polyene amphotericin B (AMB) has been reported to trigger oxidative stress in several pathogenic fungi, including C. albicans.

Deletion of the Gene in a Mutant Reverts Virulence in .

displays the ability to adapt to a wide variety of environmental conditions, triggering signaling pathways and transcriptional regulation. Sko1 is a transcription factor that was previously involved in early hypoxic response, cell wall remodeling, and stress response. In the present work, the role of mutant in o and studies was explored.

Implementation of a CRISPR-Based System for Gene Regulation in .

Clustered regularly interspaced short palindromic repeat (CRISPR) methodology is not only an efficient tool in gene editing but also an attractive platform to facilitate DNA, RNA, and protein interactions. We describe here the implementation of a CRISPR-based system to regulate expression in the clinically important yeast By fusing an allele of Cas9 devoid of nuclease activity to a transcriptional repressor (Nrg1) or activator (Gal4), we were able to show specific repression or activation of the tester gene , encoding the cytosolic catalase. We generated strains where a 1.

Overexpression of the Transcriptional Regulator Increases Susceptibility to Bile Salts and Adhesion to the Mouse Gut Mucosa in .

The transcriptional regulator Wor1 has been shown to induce the GUT transition, an environmentally triggered process that increases the fitness of in the mouse gastrointestinal tract. We have developed strains where the expression of this gene is driven from the strong and tightly regulated tetracycline promoter. These cells retain the main characteristics reported for GUT cells albeit they show defects in the initial stages of colonization.

Arsenic inorganic compounds cause oxidative stress mediated by the transcription factor PHO4 in Candida albicans.

Arsenic is a toxic metalloid widespread in nature. Recently, it has been demonstrated a main role of the transcription factor Pho4 in the acquisition of tolerance to arsenic-derived compounds, arsenite and arsenate in Candida albicans. Here, the effect of these compounds on this pathogenic yeast has been analyzed.

The Hog1 MAP Kinase Promotes the Recovery from Cell Cycle Arrest Induced by Hydrogen Peroxide in .

Eukaryotic cell cycle progression in response to environmental conditions is controlled via specific checkpoints. Signal transduction pathways mediated by MAPKs play a crucial role in sensing stress. For example, the canonical MAPKs Mkc1 (of the cell wall integrity pathway), and Hog1 (of the HOG pathway), are activated upon oxidative stress.

Role of catalase overproduction in drug resistance and virulence in Candida albicans.

Aim: To investigate the role of Cat1 overproduction in Candida albicans.

Materials & Methods: Strains overproducing the CAT1 gene were constructed.

Results: Cells overproducing CAT1 were found to be more resistant to some oxidants and mammalian phagocytic cells.

The Candida albicans Pho4 Transcription Factor Mediates Susceptibility to Stress and Influences Fitness in a Mouse Commensalism Model.

The Pho4 transcription factor is required for growth under low environmental phosphate concentrations in Saccharomyces cerevisiae. A characterization of Candida albicans pho4 mutants revealed that these cells are more susceptible to both osmotic and oxidative stress and that this effect is diminished in the presence of 5% CO2 or anaerobiosis, reflecting the relevance of oxygen metabolism in the Pho4-mediated response. A pho4 mutant was as virulent as wild type strain when assayed in the Galleria mellonella infection model and was even more resistant to murine macrophages in ex vivo killing assays.

The Mkk2 MAPKK Regulates Cell Wall Biogenesis in Cooperation with the Cek1-Pathway in Candida albicans.

The cell wall integrity pathway (CWI) plays an important role in the biogenesis of the cell wall in Candida albicans and other fungi. In the present work, the C. albicans MKK2 gene that encodes the putative MAPKK of this pathway was deleted in different backgrounds and the phenotypes of the resultant mutants were characterised.

The Pho4 transcription factor mediates the response to arsenate and arsenite in Candida albicans.

Arsenate (As (V)) is the dominant form of the toxic metalloid arsenic (As). Microorganisms have consequently developed mechanisms to detoxify and tolerate this kind of compounds. In the present work, we have explored the arsenate sensing and signaling mechanisms in the pathogenic fungus Candida albicans.

The lack of upstream elements of the Cek1 and Hog1 mediated pathways leads to a synthetic lethal phenotype upon osmotic stress in Candida albicans.

Different signal transduction pathways mediated by MAP kinases have been described in Candida albicans. These pathways sense different stimuli and, therefore, elaborate specific responses. Hog1 was identified as the MAPK that is primarily involved in stress response and virulence, while Cek1 was more specific to cell wall biogenesis, mating and biofilm formation.