Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?
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DOI：
10.1099/mgen.0.000570
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发表时间：
2021-05
影响因子：
3.9
通讯作者：
Bidula S
中科院分区：
文献类型：
--
作者：
Warner EF;Bohálová N;Brázda V;Waller ZAE;Bidula S
真菌感染每年导致超过100万人死亡，抗真菌耐药性的出现促使人们探索新的抗真菌靶点。四链体是四链核酸的二级结构，其可以调节诸如转录、翻译、复制和重组的过程。它们也存在于与微生物毒力相关的基因中，与四链体结合的配体可以消除耐药病原体。使用计算方法，我们量化了真菌界1359个基因组中的推定四链体形成序列（PQS），并探讨了它们在烟曲霉中与致病性相关的毒力，耐药性和生物学过程相关的基因中的存在。在这里，我们提出了最大的分析PQS真菌，并确定显着的异质性，这些序列在整个门，属和种。PQS在曲霉属中是遗传保守的。并且经常致病的物种似乎比它们的较小/非致病性对应物含有更少的PQS。GO-term分析表明，含PQS基因参与了锌离子结合、次生代谢产物的生物合成和转录调控等与毒力相关的过程。烟熏。虽然PQS基因组频率在A.在烟曲霉中，PQS中富含与毒力相关的基因，并且在萌发和缺氧过程中基因表达上调。此外，PQS还存在于与耐药相关的基因中。四链体可能在真菌生物学和毒力中具有重要作用，但它们的作用需要进一步阐明。
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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影响因子：
11.3
作者：
Gerwien F;Skrahina V;Kasper L;Hube B;Brunke S
通讯作者：
Brunke S
影响因子：
15.9
作者：
Brown, Alistair J. P.;Brown, Gordon D.;Netea, Mihai G.;Gow, Neil A. R.
通讯作者：
Gow, Neil A. R.
影响因子：
4.6
作者：
Bartas, Martin;Cutova, Michaela;Pecinka, Petr
通讯作者：
Pecinka, Petr
影响因子：
15
作者：
Dai, JX;Dexheimer, TS;Yang, DZ
通讯作者：
Yang, DZ
影响因子：
5.2
作者：
Bartas, Martin;Brazda, Vaclav;Pecinka, Petr
通讯作者：
Pecinka, Petr