The CgHaa1-Regulon Mediates Response and Tolerance to Acetic Acid Stress in the Human Pathogen Candida glabrata.
The CgHaa1-Regulon Mediates Response and Tolerance to Acetic Acid Stress in the Human Pathogen Candida glabrata.
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DOI：
10.1534/g3.116.034660
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发表时间：
2017-01-05
期刊：
影响因子：
--
通讯作者：
Mira NP
中科院分区：
文献类型：
--
作者：
Bernardo RT;Cunha DV;Wang C;Pereira L;Silva S;Salazar SB;Schröder MS;Okamoto M;Takahashi-Nakaguchi A;Chibana H;Aoyama T;Sá-Correia I;Azeredo J;Butler G;Mira NP
为了在酸性阴道中茁壮成长，光滑念珠菌必须科普高浓度的乙酸。C. glabrata在低pH下对乙酸的耐受性仍然很大程度上未被表征。本研究探讨了CgHaa 1转录因子（ORF CAGL 0 L 09339 g）在C. glabrata到乙酸的反应。转录组学分析表明，CgHaa 1调节，直接或间接，约75%的基因在乙酸胁迫下激活的表达。CgHaa 1激活的靶点参与多种生理功能，包括膜转运、碳水化合物和氨基酸的代谢、质膜H+-ATP酶活性的调节以及粘附。在乙酸胁迫下，CgHaa 1增加了CgPma 1质子泵的活性和表达，并有助于增加阴道上皮细胞中C.光滑的CgHAA 1和两个鉴定的CgHaa 1激活的靶点CgTPO 3和CgHSP 30在本文中被证明是C的决定因素。glabrata耐醋酸。CgTpo 3和CgHaa 1的保护作用与这些蛋白在减少C.光滑细胞在乙酸胁迫下，由CgHaa 1和其S. cerevisiae ScHaa 1直系同源物，证明了两个调控网络的明显不同的进化。这项研究的结果大大推进了对C。glabrata作为阴道殖民者。
To thrive in the acidic vaginal tract, Candida glabrata has to cope with high concentrations of acetic acid. The mechanisms underlying C. glabrata tolerance to acetic acid at low pH remain largely uncharacterized. In this work, the essential role of the CgHaa1 transcription factor (encoded by ORF CAGL0L09339g) in the response and tolerance of C. glabrata to acetic acid is demonstrated. Transcriptomic analysis showed that CgHaa1 regulates, directly or indirectly, the expression of about 75% of the genes activated under acetic acid stress. CgHaa1-activated targets are involved in multiple physiological functions including membrane transport, metabolism of carbohydrates and amino acids, regulation of the activity of the plasma membrane H+-ATPase, and adhesion. Under acetic acid stress, CgHaa1 increased the activity and the expression of the CgPma1 proton pump and contributed to increased colonization of vaginal epithelial cells by C. glabrata. CgHAA1, and two identified CgHaa1-activated targets, CgTPO3 and CgHSP30, are herein demonstrated to be determinants of C. glabrata tolerance to acetic acid. The protective effect of CgTpo3 and of CgHaa1 was linked to a role of these proteins in reducing the accumulation of acetic acid inside C. glabrata cells. In response to acetic acid stress, marked differences were found in the regulons controlled by CgHaa1 and by its S. cerevisiae ScHaa1 ortholog, demonstrating a clear divergent evolution of the two regulatory networks. The results gathered in this study significantly advance the understanding of the molecular mechanisms underlying the success of C. glabrata as a vaginal colonizer.
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影响因子：
4.1
作者：
Alves, Carlos Tiago;Silva, Sonia;Henriques, Mariana
通讯作者：
Henriques, Mariana
影响因子：
6.4
作者：
Mira NP;Palma M;Guerreiro JF;Sá-Correia I
通讯作者：
Sá-Correia I
DOI：
10.1534/g3.114.015941
发表时间：
2015-01-29
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Cottier F;Tan AS;Chen J;Lum J;Zolezzi F;Poidinger M;Pavelka N
通讯作者：
Pavelka N
影响因子：
4.1
作者：
Hueso, Guillem;Aparicio-Sanchis, Rafael;Serrano, Ramon
通讯作者：
Serrano, Ramon
影响因子：
3.2
作者：
Chattopadhyay, S;Muzaffar, NE;Pearce, DA
通讯作者：
Pearce, DA