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Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?

Fungal infections cause >1 million deaths annually and the emergence of antifungal resistance has prompted the exploration for novel antifungal targets. Quadruplexes are four-stranded nucleic acid secondary structures, which can regulate processes such as transcription, translation, replication a...

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Autores principales: Warner, Emily F., Bohálová, Natália, Brázda, Václav, Waller, Zoë A. E., Bidula, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Microbiology Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209732/
https://www.ncbi.nlm.nih.gov/pubmed/33956596
http://dx.doi.org/10.1099/mgen.0.000570
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author Warner, Emily F.
Bohálová, Natália
Brázda, Václav
Waller, Zoë A. E.
Bidula, Stefan
author_facet Warner, Emily F.
Bohálová, Natália
Brázda, Václav
Waller, Zoë A. E.
Bidula, Stefan
author_sort Warner, Emily F.
collection PubMed
description Fungal infections cause >1 million deaths annually and the emergence of antifungal resistance has prompted the exploration for novel antifungal targets. Quadruplexes are four-stranded nucleic acid secondary structures, which can regulate processes such as transcription, translation, replication and recombination. They are also found in genes linked to virulence in microbes, and ligands that bind to quadruplexes can eliminate drug-resistant pathogens. Using a computational approach, we quantified putative quadruplex-forming sequences (PQS) in 1359 genomes across the fungal kingdom and explored their presence in genes related to virulence, drug resistance and biological processes associated with pathogenicity in Aspergillus fumigatus. Here we present the largest analysis of PQS in fungi and identify significant heterogeneity of these sequences throughout phyla, genera and species. PQS were genetically conserved in Aspergillus spp. and frequently pathogenic species appeared to contain fewer PQS than their lesser/non-pathogenic counterparts. GO-term analysis identified that PQS-containing genes were involved in processes linked with virulence such as zinc ion binding, the biosynthesis of secondary metabolites and regulation of transcription in A. fumigatus. Although the genome frequency of PQS was lower in A. fumigatus, PQS could be found enriched in genes involved in virulence, and genes upregulated during germination and hypoxia. Moreover, PQS were found in genes involved in drug resistance. Quadruplexes could have important roles within fungal biology and virulence, but their roles require further elucidation.
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spelling pubmed-82097322021-06-17 Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets? Warner, Emily F. Bohálová, Natália Brázda, Václav Waller, Zoë A. E. Bidula, Stefan Microb Genom Research Articles Fungal infections cause >1 million deaths annually and the emergence of antifungal resistance has prompted the exploration for novel antifungal targets. Quadruplexes are four-stranded nucleic acid secondary structures, which can regulate processes such as transcription, translation, replication and recombination. They are also found in genes linked to virulence in microbes, and ligands that bind to quadruplexes can eliminate drug-resistant pathogens. Using a computational approach, we quantified putative quadruplex-forming sequences (PQS) in 1359 genomes across the fungal kingdom and explored their presence in genes related to virulence, drug resistance and biological processes associated with pathogenicity in Aspergillus fumigatus. Here we present the largest analysis of PQS in fungi and identify significant heterogeneity of these sequences throughout phyla, genera and species. PQS were genetically conserved in Aspergillus spp. and frequently pathogenic species appeared to contain fewer PQS than their lesser/non-pathogenic counterparts. GO-term analysis identified that PQS-containing genes were involved in processes linked with virulence such as zinc ion binding, the biosynthesis of secondary metabolites and regulation of transcription in A. fumigatus. Although the genome frequency of PQS was lower in A. fumigatus, PQS could be found enriched in genes involved in virulence, and genes upregulated during germination and hypoxia. Moreover, PQS were found in genes involved in drug resistance. Quadruplexes could have important roles within fungal biology and virulence, but their roles require further elucidation. Microbiology Society 2021-05-06 /pmc/articles/PMC8209732/ /pubmed/33956596 http://dx.doi.org/10.1099/mgen.0.000570 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
spellingShingle Research Articles
Warner, Emily F.
Bohálová, Natália
Brázda, Václav
Waller, Zoë A. E.
Bidula, Stefan
Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
title Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
title_full Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
title_fullStr Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
title_full_unstemmed Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
title_short Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
title_sort analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209732/
https://www.ncbi.nlm.nih.gov/pubmed/33956596
http://dx.doi.org/10.1099/mgen.0.000570
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