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Adnane Sellam  - - - 
Top co-authors See all
Mike Tyers

152 shared publications

Institute for Research in Immunology and Cancer (IRIC), Department of Medicine, Université de Montréal, Montréal, Québec, Canada

André Nantel

48 shared publications

National Research Council of Canada, Human Health Therapeutics, 6100 Royalmount Avenue, Montreal, QC, H4P 2R2, Canada

Jacques Corbeil

42 shared publications

Université Laval

Malcolm Whiteway

25 shared publications

Department of Biology, Concordia University, Montreal, Quebec, Canada

Michael A Cook

6 shared publications

University of Toronto

7
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Publication Record
Distribution of Articles published per year 
(2012 - 2018)
Total number of journals
published in
 
7
 
Publications See all
PREPRINT-CONTENT 0 Reads 0 Citations A phenotypic small-molecule screen identifies halogenated salicylanilides as inhibitors of fungal morphogenesis, biofilm... Carlos Garcia, Anais Burgain, Julien Chaillot, Emilie Pic, I... Published: 03 July 2018
Microbiology, doi: 10.1101/361139
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A poorly exploited paradigm in the antimicrobial therapy field is to target virulence traits for drug development. In contrast to target-focused approaches, antivirulence phenotypic screens enable identification of bioactive molecules that induce a desirable biological readout without making a priori assumption about the cellular target. Here, we screened a chemical library of 678 small molecules against the invasive hyphal growth of the human opportunistic yeast Candida albicans . We found that a halogenated salicylanilide (N1-(3,5-dichlorophenyl)-5-chloro-2-hydroxybenzamide) and one of its analog, Niclosamide, an FDA-approved anthelmintic in humans, exhibited both antifilamentation and antibiofilm activities against C. albicans and the multi-resistant yeast C. auris . The antivirulence activity of halogenated salicylanilides were also expanded to C. albicans resistant strains with different resistance mechanisms. We also found that Niclosamide protected the intestinal epithelial cells against invasion by C. albicans . Transcriptional profiling of C. albicans challenged with Niclosamide exhibited a signature that is characteristic of the mitochondria-to-nucleus retrograde response. Our chemogenomic analysis showed that halogenated salicylanilides compromise the potential-dependant mitochondrial protein translocon machinery. Given the fact that the safety of Niclosamide is well established in humans, this molecule could represent the first clinically approved antivirulence agent against a pathogenic fungus.
Article 0 Reads 1 Citation pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal Pathogen Candida albicans Julien Chaillot, Faiza Tebbji, Carlos García, Hugo Wurtele, ... Published: 09 October 2017
Frontiers in Microbiology, doi: 10.3389/fmicb.2017.01956
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Current antifungal drugs suffer from limitations including toxicity, the emergence of resistance and decreased efficacy at low pH that are typical of human vaginal surfaces. Here, we have shown that the antipsychotic drug valproic acid (VPA) exhibited a strong antifungal activity against both sensitive and resistant Candida albicans in pH condition similar to that encountered in vagina. VPA exerted a strong anti-biofilm activity and attenuated damage of vaginal epithelial cells caused by C. albicans. We also showed that VPA synergizes with the allylamine antifungal, Terbinafine. We undertook a chemogenetic screen to delineate biological processes that underlies VPA-sensitivity in C. albicans and found that vacuole-related genes were required to tolerate VPA. Confocal fluorescence live-cell imaging revealed that VPA alters vacuole integrity and support a model where alteration of vacuoles contributes to the antifungal activity. Taken together, this study suggests that VPA could be used as an effective antifungal against vulvovaginal candidiasis.
PREPRINT-CONTENT 0 Reads 1 Citation A systematic cell size screen uncovers coupling of growth to division by the p38/HOG network in Candida albicans Adnane Sellam, Julien Chaillot, Jaideep Mallick, Faiza Tebbj... Published: 14 December 2016
Cell Biology, doi: 10.1101/094144
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Cell size is a complex trait that responds to developmental and environmental cues. Quantitative analysis of the size phenome in the pathogenic yeast Candida albicans uncovered 195 genes that markedly altered cell size, few of which overlapped with known size genes in other yeast species. A potent size regulator specific to C. albicans was the conserved p38/HOG MAPK module that mediates the osmotic stress response. Basal HOG activity inhibited the SBF G1/S transcription factor complex in a stress-independent fashion to delay the G1/S transition. The HOG network also governed ribosome biogenesis through the master transcriptional regulator Sfp1. Hog1 bound to the promoters and cognate transcription factors for both the G1/S and ribosome biogenesis regulons and thereby directly linked cell growth and division. These results illuminate the evolutionary plasticity of size control and identify the HOG module as a nexus of cell cycle and growth regulation.
Article 0 Reads 0 Citations Use of phylogenetical analysis to predict susceptibility of pathogenic Candida spp. to antifungal drugs Andrée F. Maheux, Adnane Sellam, Yves Piché, Maurice Boissin... Published: 01 December 2016
Journal of Microbiological Methods, doi: 10.1016/j.mimet.2016.09.020
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PREPRINT-CONTENT 0 Reads 0 Citations Genome-wide screen for haploinsufficient cell size genes in the opportunistic yeast Candida albicans Julien Chaillot, Michael A Cook, Jacques Corbeil, Adnane Sel... Published: 28 October 2016
Genetics, doi: 10.1101/084244
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One of the most critical but still poorly understood aspects of eukaryotic cell proliferation is the basis for commitment to cell division in late G1 phase called Start in yeast and the Restriction Point in metazoans. In all species, a critical cell size threshold coordinates cell growth with cell division and thereby establishes a homeostatic cell size. While a comprehensive survey of cell size genetic determinism has been performed in the saprophytic yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, very little is known in pathogenic fungi. As a number of critical Start regulators are haploinsufficient for cell size, we applied a quantitative analysis of the size phenome, using elutriation-barcode sequencing methodology, to 5,639 barcoded heterozygous deletion strains in the opportunistic yeast Candida albicans. Our screen identified conserved known regulators and biological processes required to maintain size homeostasis in addition to novel C. albicans specific size genes, and provided a conceptual framework for future mechanistic studies. Interestingly, some of the size genes identified were required for fungal pathogenicity suggesting that cell size homeostasis may be elemental to C. albicans fitness or virulence inside the host.
Article 0 Reads 7 Citations Recent advances on Candida albicans biology and virulence Adnane Sellam, Malcolm Whiteway Published: 26 October 2016
F1000Research, doi: 10.12688/f1000research.9617.1
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Candida albicans is an important human fungal pathogen, in terms of both its clinical significance and its use as an experimental model for scientific investigation. Although this opportunistic pathogen is a natural component of the human flora, it can cause life-threatening infections in immunosuppressed patients. There are currently a limited number of antifungal molecules and drug targets, and increasing resistance to the front-line therapeutics, demonstrating a clear need for new antifungal drugs. Understanding the biology of this pathogen is an important prerequisite for identifying new drug targets for antifungal therapeutics. In this review, we highlight some recent developments that help us to understand how virulence traits are regulated at the molecular level, in addition to technical advances that improve the ability of genome editing in C. albicans.
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