Genome-wide functional analysis in<i>Candida albicans</i>

Motaung, Thabiso E.; Ells, Ruan; Pohl, Carolina H.; Albertyn, Jacobus; Tsilo, Toi J.

doi:10.1080/21505594.2017.1292198

Cited by 17 publications

(12 citation statements)

References 87 publications

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“…The GRACE collection of C. albicans conditionally lethal strains provides a powerful tool for functional genomics analysis of this important fungal pathogen ( 20 ). The background strain used for the construction of this collection, CaSS1, was developed for the specific purpose of testing the efficacy of antifungal drugs and is derived from SC5314, a clinically isolated strain; it has since been used by multiple groups to study drug interactions with Candida albicans ( 25 , 26 ; reviewed in reference 27 ). In the GRACE collection, the HIS3 marker replaces one allele of a gene of the diploid C. albicans , and the other allele is under the control of a tetracycline-responsive (TetR) promoter.…”

Section: Resultsmentioning

confidence: 99%

Chemogenomic Profiling of the Fungal Pathogen Candida albicans

Chen

Mallick

Maqnas

et al. 2018

Antimicrob Agents Chemother

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There is currently a small number of classes of antifungal drugs, and these drugs are known to target a very limited set of cellular functions. We derived a set of approximately 900 nonessential, transactivator-defective disruption strains from the tetracycline-regulated GRACE collection of strains of the fungal pathogen Candida albicans. This strain set was screened against classic antifungal drugs to identify gene inactivations that conferred either enhanced sensitivity or increased resistance to the compounds. We examined two azoles, fluconazole and posaconazole; two echinocandins, caspofungin and anidulafungin; and a polyene, amphotericin B. Overall, the chemogenomic profiles within drug classes were highly similar, but there was little overlap between classes, suggesting that the different drug classes interacted with discrete networks of genes in C. albicans. We also tested two pyridine amides, designated GPI-LY7 and GPI-C107; these drugs gave very similar profiles that were distinct from those of the echinocandins, azoles, or polyenes, supporting the idea that they target a distinct cellular function. Intriguingly, in cases where these gene sets can be compared to genetic disruptions conferring drug sensitivity in other fungi, we find very little correspondence in genes. Thus, even though the drug targets are the same in the different species, the specific genetic profiles that can lead to drug sensitivity are distinct. This implies that chemogenomic screens of one organism may be poorly predictive of the profiles found in other organisms and that drug sensitivity and resistance profiles can differ significantly among organisms even when the apparent target of the drug is the same.

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Section: Resultsmentioning

confidence: 99%

Chemogenomic Profiling of the Fungal Pathogen Candida albicans

Chen

Mallick

Maqnas

et al. 2018

Antimicrob Agents Chemother

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“…The changes in chromosome copy number in this strain may have occurred during the transformation when the deletion cassettes were introduced. Large-scale deletion collections provide wonderful resources for biological analyses (19, 25, 33–36). However, some unforeseen changes are likely to occur in some deletion strains during construction or during passaging and routine growth.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility to Medium-Chain Fatty Acids Is Associated with Trisomy of Chromosome 7 in Candida albicans

Ola

Iracane

et al. 2019

mSphere

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Aneuploidy (changes in chromosome number) and loss of heterozygosity (LOH) occur frequently in the human-pathogenic yeast Candida albicans and are associated with adaptation to stress and to antifungal drugs. Aneuploidy and LOH can also be induced during laboratory manipulations, such as during genetic transformation. We find that C. albicans strain SN152, commonly used to generate gene deletions, has undergone a major LOH event on chromosome 2. One deletion strain generated in this background has acquired extra copies of chromosomes 5 and 7. We find that trisomy (three copies) of chromosome 7 is associated with sensitivity to fatty acids.

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“…Genome-wide analyses have played important roles in discovering gene function and better understanding of the biology and pathogenesis of C. albicans (Noble and Johnson 2007;Motaung et al 2017). Several genes related to the pathogenicity of C. albicans have been described (Mayer et al 2013;Gulati and Nobile 2016;Araujo et al 2017).…”

Section: Interference With Virulence Genesmentioning

confidence: 99%

Action mechanisms of probiotics onCandidaspp. and candidiasis prevention: an update

et al. 2019

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Due to the high incidence of fungal infections caused by Candida species and their increasing resistance to antimicrobial treatments, alternative therapies such as probiotics have been studied. It has been show that several species of the genus Lactobacillus have anti-Candida activity, probably by direct inhibition, through competition for adhesion sites or production of secondary metabolites, and by indirect inhibition, through stimulation of the immune system of their host. However, the mechanisms of inhibition of these probiotics on Candida species have not yet been fully elucidated since this effect is related to more than one inhibition pathway. In the literature, several in vitro and in vivo studies have been developed seeking to elucidate the probiotics mechanisms of action. These studies have been focused on C. albicans inhibition assays, including analysis of antimicrobial activity, adherence capacity, biofilms formation, filamentation and interference on virulence genes, as well as assays of experimental candidiasis in invertebrate and vertebrate models. In this context, the purpose of this review was to gather different studies focused on the action mechanism of probiotic strains on Candida sp. and to discuss their impact on the candidiasis prevention.

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Genome-wide functional analysis inCandida albicans

Cited by 17 publications

References 87 publications

Chemogenomic Profiling of the Fungal Pathogen Candida albicans

Chemogenomic Profiling of the Fungal Pathogen Candida albicans

Susceptibility to Medium-Chain Fatty Acids Is Associated with Trisomy of Chromosome 7 in Candida albicans

Action mechanisms of probiotics onCandidaspp. and candidiasis prevention: an update

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