The role of gene copy number variation in antimicrobial resistance in human fungal pathogens

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 6, 2025

Faced with the burden of increasing resistance to antifungals in many fungal pathogens and constant emergence new drug-resistant strains, it is essential assess importance various mechanisms. Fungi have relatively plastic genomes can tolerate genomic copy number variation (CNV) caused by aneuploidy gene amplification or deletion. In cases, these changes lead adaptation stressful conditions, including those antifungal drugs. Here, we specifically examine contribution CNVs resistance. We undertook a thorough literature search, collecting reports CNV, classifying examples CNV-conferred into four main find that human pathogens, there little evidence plays major role compared other types mutations. discuss why might be underestimating their approaches being used study them.

Language: Английский

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Genome duplication in a long-term multicellularity evolution experiment.

PubMed, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

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Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012497 - e1012497

Published: Aug. 30, 2024

Antimicrobial drug resistance poses a global health threat, requiring deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex dynamics involve multiple mutations can result cooperative or competitive (clonal interference) effects. Candida albicans, major fungal pathogen, displays high rates copy number variation (CNV) and loss heterozygosity (LOH). CNV LOH events large numbers genes could synergize during adaptation. Understanding contributions antifungal adaptation is challenging, especially context whole-population genome sequencing. Here, we document sequential evolution fluconazole tolerance then C. albicans isolate involving an initial on chromosome 4, followed by R involves KSR1. Similar KSR1, which encodes reductase sphingolipid biosynthesis pathway, were also detected independently evolved resistant isolates. We dissect specific KSR1 codons affect tolerance. The combination 4 results >500-fold decrease azole susceptibility relative progenitor, illustrating compelling example rapid, yet step-wise, interplay between evolution.

Language: Английский

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Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans

Nature Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Language: Английский

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Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(10), P. 100656 - 100656

Published: Sept. 23, 2024

Language: Английский

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Fungal Stress Responses and the Importance of GPCRs

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(3), P. 213 - 213

Published: March 11, 2025

G-protein-coupled receptors (GPCRs) play a crucial role in the gene regulation of processes related to response different types stress fungi. These act as sensors extracellular signals and transmit information interior cell through G-proteins. In presence specific stresses, GPCRs activate signaling cascades that culminate activation transcription factors, which regulate expression genes associated with response, including those induced by changes environmental pH. GPCR-mediated allows fungi adapt adverse conditions such osmotic, thermal, oxidative, or nutritional stress, well fluctuations This review focuses on understanding how modulate their advancing our knowledge physiology adaptability these microorganisms changing environment.

Language: Английский

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Cellular and genetic changes during and after fluconazole exposure in Cryptococcus neoformans

International Journal of Antimicrobial Agents, Journal Year: 2025, Volume and Issue: unknown, P. 107519 - 107519

Published: April 1, 2025

Language: Английский

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Leishmania genomic adaptation: more than just a 36-body problem

Trends in Parasitology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Genome instability has been identified as a major driver of adaptation in fast-growing, eukaryotic cells, including fungi, protists, or cancer. How these cells cope with the toxic effects caused by such copy number variations remains to be elucidated. In recent years, protist parasites Leishmania spp. have emerged interesting model pathogens assess this open question and study role its intrinsic genome fitness gain culture, experimental infection, field. Here we summarize results on genomic propose thought-provoking evolutionary concepts new field that need considered when mapping genotype-to-phenotype relationships molecular epidemiological studies.

Language: Английский

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Transcriptomic and proteomic ramifications of segmental amplification in Escherichia coli

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(20)

Published: May 15, 2025

Gene amplification can drive adaptation by rapidly increasing the cellular dosage of critical gene products. Segmental amplifications often encompass large genomic regions surrounding gene(s) under selection for higher dosage. Overexpression coamplified neighboring genes imposes a substantial metabolic burden. While compensatory mutations decrease inappropriate overexpression genes, it takes time such to arise. The extent which intrinsic regulatory mechanisms modulate expression in immediate aftermath segmental is largely unknown. To address collateral effects amplification, we evolved replicate cultures an Escherichia coli mutant conditions that select inefficient enzyme whose weak activity limits growth rate. encompassing encoding weak-link arose all populations. Amplified ranged size (33 125 kb) and copy number (2 ≥14 copies). We performed RNA-seq label-free proteomics quantify amplified present at 2, 6, 14 copies. mRNA generally scales with number, but protein less well both expression. characterize molecular underlying discrepancies between several cases. also show have system-wide consequences indirectly altering nonamplified genes. Our findings indicate fitness benefit derived from depends on combined amplicon size, content, as

Language: Английский

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Integrated Disease Management, Adaptation and Genomics of Fungal Plant Pathogens in Cropping Systems

Plant Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

ABSTRACT Crop production systems contribute significantly to maintaining global food security. These often involve the cultivation of single cultivars in highly homogenised environments meet demands. Agriculturally important plant fungal pathogens can be destructive constraints such systems. Integrated disease management strategies comprising tactical use cultural, chemical and host genetic controls are deployed reduce impact pathogens. The homogenous nature these cropping combined with evolutionary forces on often‐flexible genome increases potential for rapid adaptation current integrated practices. This review explores genomic features (such as transposable elements copy number variation) that influence pathogen populations Furthermore, interactions between drive discussed relative three major components agricultural specifies need a cohesive analysis within maintain sustainable face future evolution.

Language: Английский

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