The regulatory subunits of CK2 complex mediate DNA damage response and virulence in Candida Glabrata.
The regulatory subunits of CK2 complex mediate DNA damage response and virulence in Candida Glabrata.
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DOI：
10.1186/s12866-023-03069-4
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发表时间：
2023-10-28
期刊：
影响因子：
4.2
通讯作者：
Peng, Yibing
中科院分区：
文献类型：
--
作者：
Ni, Qi;Wu, Xianwei;Su, Tongxuan;Jiang, Cen;Dong, Danfeng;Wang, Daosheng;Chen, Wei;Cui, Yingchao;Peng, Yibing
光滑念珠菌属于正常微生物群，近年来因其高患病率和耐药性而引起世界范围内的高度关注。光滑念珠菌已经发展出许多策略来逃避宿主免疫系统的清除，从而引起持续感染。尽管人们普遍认为应对诱导的 DNA 损伤很重要，但其潜在机制仍不清楚。本研究提供了迄今为止未记录的证据，证明 CgCK2 调节亚基（CgCkb1 和 CgCkb2）在 DNA 损伤反应中的重要性。 CgCKB1 或 CgCKB2 的缺失会增强细胞凋亡和 DNA 断裂，并导致细胞周期延迟。此外，在 Δckb1 和 Δckb2 菌株中观察到吞噬作用的存活缺陷。一致地，CgCKB1 和 CgCKB2 的破坏减弱了侵袭性念珠菌病小鼠模型中光滑念珠菌的毒力。此外，全局转录谱分析表明，CgCkb1 和 CgCkb2 参与细胞周期恢复和基因组稳定性。总的来说，我们的研究结果表明，对 DNA 损伤应激的反应对于光滑念珠菌在巨噬细胞中生存至关重要，从而在体内产生完全毒力。这项工作的意义在于更好地了解光滑念珠菌相关念珠菌病的致病性，并拓展临床治疗的思路。在线版本包含可在 10.1186/s12866-023-03069-4 获取的补充材料。
Candida glabrata which belongs to normal microbiota, has caused significant concern worldwide due to its high prevalence and drug resistance in recent years. C. glabrata has developed many strategies to evade the clearance of the host immune system, thereby causing persistent infection. Although coping with the induced DNA damage is widely acknowledged to be important, the underlying mechanisms remain unclear. The present study provides hitherto undocumented evidence of the importance of the regulatory subunits of CgCK2 (CgCkb1 and CgCkb2) in response to DNA damage. Deletion of CgCKB1 or CgCKB2 enhanced cellular apoptosis and DNA breaks and led to cell cycle delay. In addition, deficiencies in survival upon phagocytosis were observed in Δckb1 and Δckb2 strains. Consistently, disruption of CgCKB1 and CgCKB2 attenuated the virulence of C. glabrata in mouse models of invasive candidiasis. Furthermore, global transcriptional profiling analysis revealed that CgCkb1 and CgCkb2 participate in cell cycle resumption and genomic stability. Overall, our findings suggest that the response to DNA damage stress is crucial for C. glabrata to survive in macrophages, leading to full virulence in vivo. The significance of this work lies in providing a better understanding of pathogenicity in C. glabrata-related candidiasis and expanding ideas for clinical therapies. The online version contains supplementary material available at 10.1186/s12866-023-03069-4.
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影响因子：
5.2
作者：
Camarillo-Márquez O;Córdova-Alcántara IM;Hernández-Rodríguez CH;García-Pérez BE;Martínez-Rivera MA;Rodríguez-Tovar AV
通讯作者：
Rodríguez-Tovar AV
影响因子：
64.5
作者：
Loizou, JI;El-Khamisy, SF;Caldecott, KW
通讯作者：
Caldecott, KW
影响因子：
4.6
作者：
Castanheira, Mariana;Deshpande, Lalitagauri M.;Pfaller, Michael A.
通讯作者：
Pfaller, Michael A.
影响因子：
7.5
作者：
Friedel, Anna M.;Pike, Brietta L.;Gasser, Susan M.
通讯作者：
Gasser, Susan M.
影响因子：
2.6
作者：
Janeczko, Monika;Maslyk, Maciej;Golczyk, Hieronim
通讯作者：
Golczyk, Hieronim