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虫媒白僵菌在巨噬细胞感染过程中的时间转录反应揭示了一个多功能转录调控因子 CgXbp1，该因子对巨噬细胞反应和氟康唑耐药性非常重要。

Temporal transcriptional response of during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and fluconazole resistance.

机构信息

Faculty of Health Sciences, University of Macau, Taipa, China.

Gene Expression, Genomics and Bioinformatics Core, Faculty of Health Sciences, University of Macau, Taipa, China.

出版信息

Elife. 2024 Oct 2;13:e73832. doi: 10.7554/eLife.73832.

DOI:10.7554/eLife.73832
PMID:39356739
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11554308/
Abstract

can thrive inside macrophages and tolerate high levels of azole antifungals. These innate abilities render infections by this human pathogen a clinical challenge. How reacts inside macrophages and what is the molecular basis of its drug tolerance are not well understood. Here, we mapped genome-wide RNA polymerase II (RNAPII) occupancy in to delineate its transcriptional responses during macrophage infection in high temporal resolution. RNAPII profiles revealed dynamic responses to macrophages with genes of specialized pathways activated chronologically at different times of infection. We identified an uncharacterized transcription factor (CgXbp1) important for the chronological macrophage response, survival in macrophages, and virulence. Genome-wide mapping of CgXbp1 direct targets further revealed its multi-faceted functions, regulating not only virulence-related genes but also genes associated with drug resistance. Finally, we showed that CgXbp1 indeed also affects fluconazole resistance. Overall, this work presents a powerful approach for examining host-pathogen interaction and uncovers a novel transcription factor important for 's survival in macrophages and drug tolerance.

摘要

能够在巨噬细胞内生存，并耐受高水平的唑类抗真菌药物。这些先天能力使得这种人类病原体的感染成为临床挑战。 在巨噬细胞内如何反应，以及其药物耐受的分子基础尚不清楚。在这里，我们绘制了 中全基因组 RNA 聚合酶 II（RNAPII）占据图谱，以在高时间分辨率描绘其在巨噬细胞感染期间的转录反应。RNAPII 图谱显示，随着感染时间的不同，专门途径的基因按时间顺序被激活，对巨噬细胞的 反应具有动态性。我们确定了一个未被表征的转录因子（CgXbp1），对于巨噬细胞的时间反应、在巨噬细胞中的存活和毒力很重要。CgXbp1 直接靶标的全基因组作图进一步揭示了其多方面的功能，不仅调节与毒力相关的基因，还调节与耐药性相关的基因。最后，我们表明 CgXbp1 确实也影响氟康唑耐药性。总的来说，这项工作提供了一种强大的方法来研究宿主-病原体相互作用，并揭示了一个对 在巨噬细胞中生存和药物耐受很重要的新型转录因子。

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