Trehalose 6-phosphate phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus.
Trehalose 6-phosphate phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus.
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DOI：
10.1111/j.1365-2958.2010.07254.x
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发表时间：
2010-08
影响因子：
3.6
通讯作者：
Cramer RA Jr
中科院分区：
文献类型：
--
作者：
Puttikamonkul S;Willger SD;Grahl N;Perfect JR;Movahed N;Bothner B;Park S;Paderu P;Perlin DS;Cramer RA Jr
海藻糖生物合成途径对于人类和植物真菌病原体的毒力至关重要。在本研究中，我们测试了烟曲霉毒力需要海藻糖 6-磷酸磷酸酶 (T6PP) 的假设。当烟曲霉 T6PP 的突变体 OrlA 在葡萄糖 (1%) 基本培养基上生长时，表现出与无性繁殖相关的严重形态缺陷。这些缺陷可以通过添加渗透稳定剂、降低孵育温度或增加葡萄糖水平（>4%）来弥补。随后用细胞壁扰动剂对突变体进行的检查揭示了细胞壁生物合成与海藻糖-6-磷酸（T6P）水平之间的联系。正如预期的那样，在 OrlA 不存在的情况下，高水平的 T6P 积累，导致游离无机磷酸盐 (Pi) 耗尽并抑制己糖激酶活性。令人惊讶的是，在没有 OrlA 的情况下，海藻糖的产生仍然持续。进一步的分析表明，烟曲霉含有两种海藻糖磷酸化酶，它们可能负责在 OrlA 不存在的情况下产生海藻糖。尽管在体外生长条件下生长速率正常，但orlA突变体在两种不同的侵袭性肺曲霉病小鼠模型中实际上是无毒的。我们的结果表明，对该途径的进一步研究将为真菌细胞壁生物合成和毒力的调节带来新的见解。
The trehalose biosynthesis pathway is critical for virulence in human and plant fungal pathogens. In this study, we tested the hypothesis that trehalose-6-phosphate phosphatase (T6PP) is required for Aspergillus fumigatus virulence. A mutant of the A. fumigatus T6PP, OrlA, displayed severe morphological defects related to asexual reproduction when grown on glucose (1%) minimal media. These defects could be rescued by addition of osmotic stabilizers, reduction in incubation temperature, or increase in glucose levels (>4%). Subsequent examination of the mutant with cell wall perturbing agents revealed a link between cell wall biosynthesis and trehalose-6-phosphate (T6P) levels. As expected, high levels of T6P accumulated in the absence of OrlA resulting in depletion of free inorganic phosphate (Pi) and inhibition of hexokinase activity. Surprisingly, trehalose production persisted in the absence of OrlA. Further analyses revealed that A. fumigatus contains two trehalose phosphorylases that may be responsible for trehalose production in the absence of OrlA. Despite a normal growth rate under in vitro growth conditions, the orlA mutant was virtually avirulent in two distinct murine models of invasive pulmonary aspergillosis. Our results suggest that further study of this pathway will lead to new insights into regulation of fungal cell wall biosynthesis and virulence.
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影响因子：
2.8
作者：
Fillinger, S;Chaveroche, MK;d'Enfert, C
通讯作者：
d'Enfert, C
影响因子：
2.1
作者：
AISAKA, K;MASUDA, T
通讯作者：
MASUDA, T
DOI：
10.1111/j.1432-1033.1974.tb03659.x
发表时间：
1974-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BELOCOPITOW, E;MARECHAL, LR
通讯作者：
MARECHAL, LR
海藻糖是白色念珠菌 Cap1p 氧化应激反应的重要介质。
影响因子：
2
作者：
Cao, YingYing;Wang, Yan;Zhang, GuoQing
通讯作者：
Zhang, GuoQing
影响因子：
3.4
作者：
Avonce N;Mendoza-Vargas A;Morett E;Iturriaga G
通讯作者：
Iturriaga G