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1.
PLoS Genet ; 18(12): e1010576, 2022 12.
Article in English | MEDLINE | ID: mdl-36574460

ABSTRACT

A delicate balance between genome stability and instability ensures genome integrity while generating genetic diversity, a critical step for evolution. Indeed, while excessive genome instability is harmful, moderated genome instability can drive adaptation to novel environments by maximising genetic variation. Candida albicans, a human fungal pathogen that colonises different parts of the human body, adapts rapidly and frequently to different hostile host microenvironments. In this organism, the ability to generate large-scale genomic variation is a key adaptative mechanism triggering dangerous infections even in the presence of antifungal drugs. Understanding how fitter novel karyotypes are selected is key to determining how C. albicans and other microbial pathogens establish infections. Here, we identified the SUMO protease Ulp2 as a regulator of C. albicans genome integrity through genetic screening. Deletion of ULP2 leads to increased genome instability, enhanced genome variation and reduced fitness in the absence of additional stress. The combined stress caused by the lack of ULP2 and antifungal drug treatment leads to the selection of adaptive segmental aneuploidies that partially rescue the fitness defects of ulp2Δ/Δ cells. Short and long-read genomic sequencing demonstrates that these novel genotypes are selected via a two-step process leading to the formation of novel chromosomal fragments with breakpoints at microhomology regions and DNA repeats.


Subject(s)
Candida albicans , Peptide Hydrolases , Aneuploidy , Antifungal Agents , Candida albicans/genetics , Endopeptidases/genetics , Genomic Instability/genetics , Peptide Hydrolases/genetics
2.
Pathogens ; 10(11)2021 Nov 11.
Article in English | MEDLINE | ID: mdl-34832617

ABSTRACT

The human fungal pathogen Candida albicans is a dimorphic opportunistic pathogen that colonises most of the human population without creating any harm. However, this fungus can also cause life-threatening infections in immunocompromised individuals. The ability to successfully colonise different host niches is critical for establishing infections and pathogenesis. C. albicans can live and divide in various morphological forms critical for its survival in the host. Indeed, C. albicans can grow as both yeast and hyphae and can form biofilms containing hyphae. The transcriptional regulatory network governing the switching between these different forms is complex but well understood. In contrast, non-DNA based epigenetic modulation is emerging as a crucial but still poorly studied regulatory mechanism of morphological transition. This review explores our current understanding of chromatin-mediated epigenetic regulation of the yeast to hyphae switch and biofilm formation. We highlight how modification of chromatin structure and non-coding RNAs contribute to these morphological transitions.

3.
mBio ; 12(5): e0187121, 2021 10 26.
Article in English | MEDLINE | ID: mdl-34488452

ABSTRACT

Microorganisms need to adapt to environmental changes, and genome plasticity can lead to rapid adaptation to hostile environments by increasing genetic diversity. Here, we investigate genome plasticity in the CTG(Ser1) yeast Scheffersomyces stipitis, an organism with an enormous potential for second-generation biofuel production. We demonstrate that S. stipitis has an intrinsically plastic genome and that different S. stipitis isolates have genomes with distinct chromosome organizations. Real-time evolution experiments show that S. stipitis genome plasticity is common and rapid since extensive genomic changes with fitness benefits are detected following in vitro evolution experiments. Hybrid MinION Nanopore and Illumina genome sequencing identify retrotransposons as major drivers of genome diversity. Indeed, the number and position of retrotransposons are different in different S. stipitis isolates, and retrotransposon-rich regions of the genome are sites of chromosome rearrangements. Our findings provide important insights into the adaptation strategies of the CTG(Ser1) yeast clade and have critical implications in the development of second-generation biofuels. These data highlight that genome plasticity is an essential factor for developing sustainable S. stipitis platforms for second-generation biofuels production. IMPORTANCE Genomes contain genes encoding the information needed to build the organism and allow it to grow and develop. Genomes are described as stable structures where genes have specific positions within a chromosome. Changes in gene dosage and position are viewed as harmful. However, it is becoming increasingly clear that genome plasticity can benefit microbial organisms that need to adapt rapidly to environmental changes. Mechanisms of genome plasticity are still poorly understood. This study focuses on Scheffersomyces stipitis, a yeast that holds great potential for second-generation biofuel production generated from forestry and agriculture waste. We demonstrate that S. stipitis chromosomes are easily reshuffled and that chromosome reshuffling is linked to adaptation to hostile environments. Genome sequencing demonstrates that mobile genetic elements, called transposons, mediate S. stipitis genome reshuffling. These data highlight that understanding genome plasticity is important for developing sustainable S. stipitis platforms for second-generation biofuels production.


Subject(s)
Genome, Bacterial , Plastics , Saccharomycetales/genetics , Biofuels , Fermentation , Phenotype , Retroelements , Saccharomycetales/classification , Saccharomycetales/isolation & purification , Saccharomycetales/metabolism
4.
Plant Physiol Biochem ; 149: 256-265, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32087537

ABSTRACT

Chemical stimulants, used to enhance biomass yield, are highly desirable for the commercialisation of algal products for a wide range of applications in the food, pharma and biofuels sectors. In the present study, phenolic compounds, varying in substituents and positional isomers on the arene ring have been evaluated to determine structure-activity relationship and growth. The phenols, catechol, 4-methylcatechol and 2, 4-dimethyl phenol were generally inhibitory to growth as were the compounds containing an aldehyde function. By contrast, the phenolic acids, salicylic acid, aspirin and 4-hydroxybenzoate markedly stimulated cell proliferation enhancing cell numbers by 20-45% at mid-log phase. The order of growth stimulation was ortho > para > meta with respect to the position of the OH group. Both SA and aspirin reduced 16:3 in chloroplast galactolipids. In addition, both compounds inhibited lipoxygenase activity and lowered the levels of lipid hydroperoxides and malondialdehydes in the cells. The present study has demonstrated the possibility of using SA or aspirin to promote algal growth through the manipulation of lipid metabolising enzymes.


Subject(s)
Aspirin , Chlamydomonas , Salicylic Acid , Aspirin/pharmacology , Chlamydomonas/drug effects , Chloroplasts/drug effects , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Fatty Acid Desaturases/metabolism , Lipoxygenase/metabolism , Salicylic Acid/pharmacology
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