Chromatin-Mediated Regulation of Genome Plasticity in Human Fungal Pathogens

Buscaino, Alessia

doi:10.3390/genes10110855

Cited by 28 publications

(32 citation statements)

References 131 publications

(173 reference statements)

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“…The same biochemical or genetic plasticity which enables fungi to adapt to stressors ranging from climate changes and nutrient availability to internalized toxins from competing microbiota can also allow for adaptation to antifungals (Verweij et al, 2016a;Hokken et al 2019;Buil et al 2019;Covo 2020). Loss of genetic stability in fungal species such as Candida albicans and A. fumigatus has been associated with lessened susceptibility to triazole antifungals (Selmecki et al, 2009;Buscaino, 2019). While frequent genomic changes can often result in inviable or weakened isolates under normal conditions, a moderate level of genetic instability can allow for selection of isolates inherently resistant to an adverse condition (Verweij et al, 2016b;Dos Reis et al, 2018;Buscaino, 2019).…”

Section: Target Gene Mutation-independent Resistancementioning

confidence: 99%

“…2019; Covo 2020). Loss of genetic stability in fungal species such as Candida albicans and A. fumigatus has been associated with lessened susceptibility to triazole antifungals (Selmecki et al ., 2009; Buscaino, 2019). While frequent genomic changes can often result in inviable or weakened isolates under normal conditions, a moderate level of genetic instability can allow for selection of isolates inherently resistant to an adverse condition (Verweij et al ., 2016b; Dos Reis et al ., 2018; Buscaino, 2019).…”

Section: The Rise Of Resistancementioning

confidence: 99%

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Mechanisms of triazole resistance in Aspergillus fumigatus

Nywening

Rybak

Rogers

et al. 2020

Environmental Microbiology

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The ubiquitous fungal pathogen Aspergillus fumigatus is the primary cause of opportunistic mould infections in humans. Aspergilli disseminate via asexual conidia passively travelling through air currents to germinate within a broad range of environs, wherever suitable nutrients are found. Though the average human inhales hundreds of conidia daily, A. fumigatus invasive infections primarily affect the immunocompromised. At-risk individuals can develop often fatal invasive disease for which therapeutic options are limited. Regrettably, the global insurgence of isolates resistant to the triazoles, the frontline antifungal class used in medicine and agriculture to control A. fumigatus, is complicating the treatment of patients. Triazole antifungal resistance in A. fumigatus has become recognized as a global, yet poorly comprehended, problem. Due to a multitude of factors, the magnitude of resistant infections and their contribution to treatment outcomes are likely underestimated. Current studies suggest that human drug-resistant infections can be either environmentally acquired or de novo host selected during patient therapy. While much concerning development of resistance is yet unknown, recent investigations have revealed assorted underlying mechanisms enabling triazole resistance within individual clinical and environmental isolates. This review will provide an overview of triazole resistance as it is currently understood, as well as highlight some of the prominent biological mechanisms associated with clinical and environmental resistance to triazoles in A. fumigatus.

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Section: Target Gene Mutation-independent Resistancementioning

confidence: 99%

Section: The Rise Of Resistancementioning

confidence: 99%

Mechanisms of triazole resistance in Aspergillus fumigatus

Nywening

Rybak

Rogers

et al. 2020

Environmental Microbiology

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“…It is well established that genome plasticity is a critical adaptive mechanism in one member of the CTG (Ser1)-clade: the human fungal pathogens Candida albicans (29). C. albicans has a diploid genome organised in 8 chromosomes.…”

Section: Retrotransposons Can Be Further Classified Into Long Terminamentioning

confidence: 99%

“…However, the genome of eukaryotic microorganisms is plastic and can adopt different chromosomal organisations. Indeed, genome instability can be beneficial in microbial organisms that need to adapt rapidly and reversibly to changing environments (26)(27)(28)(29). This is because genomic instability can increase genetic diversity, thereby allowing selection of genotype(s) better adapted in a new environment.…”

Section: Introductionmentioning

confidence: 99%

The genome of the CTG(Ser1) yeast Scheffersomyces stipitisis plastic

Estevez

Armitage

Bates

et al. 2021

Preprint

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Microorganisms need to adapt to environmental changes, and genome plasticity can lead to adaptation by increasing genetic diversity. The CTG (Ser1) clade of fungi is a diverse yeast group that can adapt remarkably well to hostile environments. Genome plasticity has emerged as a critical regulatory mechanism, in one member of the (Ser1) clade: the human fungal pathogen Candida albicans . However, in many aspects, C. albicans differs from other CTG (Ser1) members as it lacks a canonical sexual cycle and is an obligatory commensal. It is still unknown whether environmental CTG (Ser1) fungi with a canonical sexual cycle utilise genome plasticity as a strategy for adaptation. To address this question, we investigated genome plasticity in the CTG (Ser1) yeast Scheffersomyces stipitis. The non-pathogenic S. stipitis yeast does not live in the human host and has a canonical sexual cycle. We demonstrated that the S. stipitis genome is intrinsically unstable. Different natural isolates have a genome with a dissimilar chromosomal organisation, and extensive genomic changes are detected following in vitro evolution experiments. Hybrid MinION Nanopore and Illumina genome sequencing demonstrate that retrotransposons are major drivers of genome diversity and that variation in genes encoding adhesin-like proteins is linked to distinct phenotypes.

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“…The mechanism by which such stress-induced mutagenesis arises remains to be determined, but taken together these findings suggest that regulators of genome architecture and chromatin structure may play a role in this process. Indeed heterochromatin, or densely packed chromatin structure, is recognized as a facilitator of genome plasticity in multiple fungal species [ 69 ]. One very interesting question would be whether H3K56ac levels are altered during stress induced mutagenesis in Candida spp.…”

Section: Chromatin Structure and The Availability Of Anti-fungal Rmentioning

confidence: 99%

Chromatin Structure and Drug Resistance in Candida spp.

O'Kane

Weild

Hyland

2020

JoF

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Anti-microbial resistance (AMR) is currently one of the most serious threats to global human health and, appropriately, research to tackle AMR garnishes significant investment and extensive attention from the scientific community. However, most of this effort focuses on antibiotics, and research into anti-fungal resistance (AFR) is vastly under-represented in comparison. Given the growing number of vulnerable, immunocompromised individuals, as well as the positive impact global warming has on fungal growth, there is an immediate urgency to tackle fungal disease, and the disturbing rise in AFR. Chromatin structure and gene expression regulation play pivotal roles in the adaptation of fungal species to anti-fungal stress, suggesting a potential therapeutic avenue to tackle AFR. In this review we discuss both the genetic and epigenetic mechanisms by which chromatin structure can dictate AFR mechanisms and will present evidence of how pathogenic yeast, specifically from the Candida genus, modify chromatin structure to promote survival in the presence of anti-fungal drugs. We also discuss the mechanisms by which anti-chromatin therapy, specifically lysine deacetylase inhibitors, influence the acquisition and phenotypic expression of AFR in Candida spp. and their potential as effective adjuvants to mitigate against AFR.

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Chromatin-Mediated Regulation of Genome Plasticity in Human Fungal Pathogens

Cited by 28 publications

References 131 publications

Mechanisms of triazole resistance in Aspergillus fumigatus

Mechanisms of triazole resistance in Aspergillus fumigatus

The genome of the CTG(Ser1) yeast Scheffersomyces stipitisis plastic

Chromatin Structure and Drug Resistance in Candida spp.

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