Indole-3-acetic acid synthesized through the indole-3-pyruvate pathway promotes Candida tropicalis biofilm formation.

Indole-3-acetic acid synthesized through the indole-3-pyruvate pathway promotes Candida tropicalis biofilm formation.
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通过吲哚-3-丙酮酸途径合成的吲哚-3-乙酸促进了热带念珠菌生物膜的形成。

DOI:
10.1371/journal.pone.0244246
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发表时间:
2020
期刊:
影响因子:
3.7
通讯作者:
Ghannoum MA
Ghannoum MA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miyagi M;Wilson R;Saigusa D;Umeda K;Saijo R;Hager CL;Li Y;McCormick T;Ghannoum MA

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我们之前发现,在克罗恩病患者中,真菌热带念珠菌的丰度升高与大肠杆菌和粘质沙雷氏菌呈正相关,当这三种病原体共同培养时,形成了一个强大的混合物种生物膜。这一发现表明,这三种病原体可能通过分泌小信号分子进行交流并促进生物膜的形成。为了确定候选信号分子,我们对三种病原体的单种和三种培养物进行了代谢组学分析。该分析确定了15种代谢物在三种培养中高度增加。一种高度诱导的代谢物是吲哚-3-乙酸(IAA),它已被证明能诱导某些真菌成丝。因此,我们测试了IAA对热带镰刀菌生物膜形成的影响,证明IAA促进了热带镰刀菌生物膜的形成。然后,我们以13c标记的色氨酸为前体进行同位素示踪实验,揭示了热带葡萄中IAA的生物合成途径。结果表明,热带木霉通过吲哚-3-丙酮酸途径合成IAA。使用吲哚-3-丙酮酸途径抑制剂的进一步研究有必要破译IAA影响生物膜形成的机制。
We previously found that the elevated abundance of the fungus Candida tropicalis is positively correlated with the bacteria Escherichia coli and Serratia marcescens in Crohn’s disease patients and the three pathogens, when co-cultured, form a robust mixed-species biofilm. The finding suggests that these three pathogens communicate and promote biofilm formation, possibly through secretion of small signaling molecules. To identify candidate signaling molecules, we carried out a metabolomic analysis of the single-species and triple-species cultures of the three pathogens. This analysis identified 15 metabolites that were highly increased in the triple-species culture. One highly induced metabolite was indole-3-acetic acid (IAA), which has been shown to induce filamentation of certain fungi. We thus tested the effect of IAA on biofilm formation of C. tropicalis and demonstrated that IAA promotes biofilm formation of C. tropicalis. Then, we carried out isotope tracing experiments using 13C-labeled-tryptophan as a precursor to uncover the biosynthesis pathway of IAA in C. tropicalis. The results indicated that C. tropicalis synthesizes IAA through the indole-3-pyruvate pathway. Further studies using inhibitors of the indole-3-pyruvate pathway are warranted to decipher the mechanisms by which IAA influences biofilm formation.
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