دورية أكاديمية
أعرض في EDS

A trade-off between proliferation and defense in the fungal pathogen Cryptococcus at alkaline pH is controlled by the transcription factor GAT201.

التفاصيل البيبلوغرافية
العنوان: A trade-off between proliferation and defense in the fungal pathogen Cryptococcus at alkaline pH is controlled by the transcription factor GAT201.
المؤلفون: Hughes ES; Institute for Cell Biology, and Centre for Engineering Biology, School of Biological Sciences, The University of Edinburgh., Tuck LR; Institute for Cell Biology, and Centre for Engineering Biology, School of Biological Sciences, The University of Edinburgh., He Z; Institute for Cell Biology, and Centre for Engineering Biology, School of Biological Sciences, The University of Edinburgh., Ballou ER; MRC Centre for Medical Mycology, The University of Exeter., Wallace EWJ; Institute for Cell Biology, and Centre for Engineering Biology, School of Biological Sciences, The University of Edinburgh.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 11. Date of Electronic Publication: 2024 Jun 11.
نوع المنشور: Journal Article; Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Cryptococcus is a fungal pathogen whose virulence relies on proliferation in and dissemination to host sites, and on synthesis of a defensive yet metabolically costly polysaccharide capsule. Regulatory pathways required for Cryptococcus virulence include a GATA-like transcription factor, Gat201, that regulates Cryptococcal virulence in both capsule-dependent and capsule-independent ways. Here we show that Gat201 is part of a negative regulatory pathway that limits fungal survival at alkaline pH. RNA-seq analysis found strong induction of GAT201 expression within minutes of transfer to RPMI media at alkaline pH. Microscopy, growth curves, and colony forming unit assays show that in RPMI at alkaline pH wild-type Cryptococcus neoformans yeast cells produce capsule but do not bud or maintain viability, while gat201Δ cells make buds and maintain viability, yet fail to produce capsule. GAT201 is required for transcriptional upregulation of a specific set of genes, the majority of which are direct Gat201 targets. Evolutionary analysis shows that Gat201 is in a subfamily of GATA-like transcription factors that is conserved within pathogenic fungi but absent in model yeasts. This work identifies the Gat201 pathway as controlling a trade-off between proliferation and production of defensive capsule. The assays established here will allow characterisation of the mechanisms of action of the Gat201 pathway. Together, our findings urge improved understanding of the regulation of proliferation as a driver of fungal pathogenesis.
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; R01 AI100272 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20230703 Latest Revision: 20240628
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10312749
DOI: 10.1101/2023.06.14.543486
PMID: 37398450
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2023.06.14.543486