Cell surface changes in the Candida albicans mitochondrial mutant goa1Δ are associated with reduced recognition by innate immune cells.
Cell surface changes in the Candida albicans mitochondrial mutant goa1Δ are associated with reduced recognition by innate immune cells.
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DOI：
10.1111/cmi.12135
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发表时间：
2013-09
影响因子：
3.4
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
She X;Zhang L;Chen H;Calderone R;Li D
我们以前已经鉴定了几种来自人类病原体白色念珠菌的真菌特异性蛋白，它们要么编码电子传递链(ETC)的线粒体复合体I(CI)亚单位，要么调节CI活性(Goa1p)。在此，我们研究了线粒体突变体goa1Δ中能量产生和细胞壁基因表达的作用。我们发现，GoA1Δ中细胞壁编码基因的下调导致了对刚果红和钙氟白等细胞壁抑制剂的敏感性，减少了巨噬细胞系的吞噬功能，减少了巨噬细胞受体的识别，并减少了IL-6、IL-10和干扰素-γ等细胞因子的表达。尽管巨噬细胞的识别能力降低，但GoA1Δ的杀伤力仍与对照菌株相同。我们还证明，在GoA1Δ存在的情况下，上皮细胞受体E-钙粘素和表皮生长因子受体的表达也会减少。总之，我们的数据证明了线粒体在细胞壁生物分子的表达以及白念珠菌与天然免疫和上皮细胞的相互作用中的重要性。我们的基本前提是，Goa1p等线粒体蛋白和其他真菌特有的线粒体蛋白调节细胞生长和毒力的关键功能。因此，它们仍然是抗真菌药物发现的有效药物靶点。
We have previously characterized several fungal-specific proteins from the human pathogen Candida albicans that either encode subunits of mitochondria Complex I (CI) of the electron transport chain (ETC) or regulate CI activity (Goa1p). Herein, the role of energy production and cell wall gene expression is investigated in the mitochondria mutant goa1Δ. We show that down regulation of cell wall-encoding genes in the goa1Δ results in sensitivity to cell wall inhibitors such as congo red and calcofluor white, reduced phagocytosis by a macrophage cell line, reduced recognition by macrophage receptors, and decreased expression of cytokines such as IL-6, IL-10, and IFN-γ. In spite of the reduced recognition by macrophages, the goa1Δ is still killed to the same extent as control strains. We also demonstrate that expression of the epithelial cell receptors E-cadherin and EGFR is also reduced in the presence of goa1Δ. Together, our data demonstrate the importance of mitochondria in the expression of cell wall biomolecules and the interaction of C. albicans with innate immune and epithelial cells. Our underlying premise is that mitochondrial proteins such as Goa1p and other fungal-specific mitochondrial proteins regulate critical functions in cell growth and in virulence. As such, they remain as valid drug targets for antifungal drug discovery.
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DOI：
10.1086/523110
发表时间：
2007-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Gow NA;Netea MG;Munro CA;Ferwerda G;Bates S;Mora-Montes HM;Walker L;Jansen T;Jacobs L;Tsoni V;Brown GD;Odds FC;Van der Meer JW;Brown AJ;Kullberg BJ
通讯作者：
Kullberg BJ
影响因子：
6.7
作者：
Lewis LE;Bain JM;Lowes C;Gillespie C;Rudkin FM;Gow NA;Erwig LP
通讯作者：
Erwig LP
影响因子：
--
作者：
Bambach, Adrienne;Fernandes, Mariana P.;Calderone, Richard
通讯作者：
Calderone, Richard
影响因子：
3.1
作者：
Cheng, G;Wozniak, K;Hoyer, LL
通讯作者：
Hoyer, LL
影响因子：
--
作者：
Lorenz, MC;Bender, JA;Fink, GR
通讯作者：
Fink, GR