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

Warner, EF; Bohálová, N; Brázda, V; Waller, ZAE; Bidula, S; (2021) Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets? Microbial Genomics , 7 (5) , Article 000570. 10.1099/mgen.0.000570. Green open access

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Abstract

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.

Type: Article
Title: Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1099/mgen.0.000570
Publisher version: https://doi.org/10.1099/mgen.0.000570
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/deed.ast). This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Keywords: Fungi, in-silico, virulence, drug resistance, Aspergillus fumigatus, G-quadruplexes, i-motifs
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10127613
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