Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
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 weremore »
- Authors:
-
[3];
[4];
[5]
- Univ. of Cambridge (United Kingdom); Ikarovec Limited, Norwich (United Kingdom)
- Czech Academy of Sciences, Brno (Czechia); Masaryk Univ., Brno (Czechia)
- Czech Academy of Sciences, Brno (Czechia)
- Univ. College London (United Kingdom)
- Univ. of East Anglia, Norwich (United Kingdom)
- Publication Date:
- Research Org.:
- Univ. of California, Oakland, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1816296
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Microbial Genomics
- Additional Journal Information:
- Journal Volume: 7; Journal Issue: 5; Journal ID: ISSN 2057-5858
- Publisher:
- Society for General Microbiology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Fungi; in-silico; virulence; drug resistance; Aspergillus fumigatus; G-quadruplexes; i-motifs
Citation Formats
Warner, Emily F., Bohálová, Natália, Brázda, Václav, Waller, Zoë A. E., and Bidula, Stefan. Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?. United States: N. p., 2021.
Web. doi:10.1099/mgen.0.000570.
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?. United States. https://doi.org/10.1099/mgen.0.000570
Warner, Emily F., Bohálová, Natália, Brázda, Václav, Waller, Zoë A. E., and Bidula, Stefan. Thu .
"Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?". United States. https://doi.org/10.1099/mgen.0.000570. https://www.osti.gov/servlets/purl/1816296.
@article{osti_1816296,
title = {Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?},
author = {Warner, Emily F. and Bohálová, Natália and Brázda, Václav and Waller, Zoë A. E. and Bidula, Stefan},
abstractNote = {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.},
doi = {10.1099/mgen.0.000570},
journal = {Microbial Genomics},
number = 5,
volume = 7,
place = {United States},
year = {Thu May 06 00:00:00 EDT 2021},
month = {Thu May 06 00:00:00 EDT 2021}
}
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