School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Present address: Ikarovec Limited, Norwich Research Park Innovation Centre, Norwich, UK.
Microb Genom. 2021 May;7(5). doi: 10.1099/mgen.0.000570.
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 . 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 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 . Although the genome frequency of PQS was lower in , 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.
真菌性感染每年导致超过 100 万人死亡，抗真菌药物耐药性的出现促使人们探索新的抗真菌靶点。四链体是一种四条链的核酸二级结构，可以调节转录、翻译、复制和重组等过程。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。我们使用计算方法在真菌界的 1359 个基因组中量化了假定的四链体形成序列（PQS），并探索了它们在与毒力、耐药性以及与致病性相关的生物学过程相关的基因中的存在。在此，我们提出了真菌中 PQS 的最大分析，并确定了这些序列在门、属和种之间存在显著的异质性。PQS 在 种中具有遗传保守性，而频繁出现的致病性物种似乎比它们的低致病性/非致病性对应物含有更少的 PQS。GO-term 分析表明，含有 PQS 的基因参与与毒力相关的过程，如锌离子结合、次生代谢物的生物合成以及转录调控。尽管 PQS 在 中的基因组频率较低，但可以发现 PQS 富集在与毒力相关的基因中，以及在萌发和缺氧期间上调的基因中。此外，PQS 存在于与耐药性相关的基因中。四链体可能在真菌生物学和毒力中发挥重要作用，但它们的作用需要进一步阐明。
