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新型隐球菌中TUP1的破坏揭示了一种肽介导的密度依赖性生长现象,该现象类似于群体感应。

TUP1 disruption in Cryptococcus neoformans uncovers a peptide-mediated density-dependent growth phenomenon that mimics quorum sensing.

作者信息

Lee Hyeseung, Chang Yun C, Nardone Glenn, Kwon-Chung Kyung J

机构信息

Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA.

出版信息

Mol Microbiol. 2007 May;64(3):591-601. doi: 10.1111/j.1365-2958.2007.05666.x.

DOI:10.1111/j.1365-2958.2007.05666.x
PMID:17462010
Abstract

Cryptococcus neoformans is a pathogenic yeast that causes life-threatening meningoencephalitis and grows well on mycological media regardless of inoculum size. Interestingly, a deletion of the global repressor TUP1 in C. neoformans uncovered a density-dependent growth phenotype reminiscent of the quorum-sensing phenomenon. An inoculum size of lower than 10(3) cells of the tup1Delta strain failed to form colonies on agar media while inocula of 10(5)-10(6) cells per plate formed a lawn. This phenotype, expressed as the inability to grow at low cell densities, was rescued by the culture filtrate from a high cell density tup1Delta culture and the active molecule in this culture filtrate was identified to be an oligopeptide composed of 11 amino acids. Activity assays, using a synthetic version of the peptide with strains harbouring a deletion of the corresponding gene, proved that the oligopeptide functioned as an autoregulatory molecule responsible for the density-dependent phenotype. Although a density-dependent growth phenotype has been reported in several species of Ascomycetes, no peptide has been reported to function as an autoregulator in the Kingdom Fungi. The identification of an 11-mer peptide as an autoregulatory molecule in C. neoformans suggests that a diverse mechanism of cell-to-cell communication exists in the Kingdom Fungi.

摘要

新型隐球菌是一种致病性酵母,可引发危及生命的脑膜脑炎,且无论接种量大小,在真菌培养基上均能良好生长。有趣的是,新型隐球菌中全局阻遏因子TUP1的缺失揭示了一种密度依赖性生长表型,类似于群体感应现象。tup1Δ菌株接种量低于10³个细胞时无法在琼脂培养基上形成菌落,而每平板接种10⁵ - 10⁶个细胞则形成菌苔。这种表现为在低细胞密度下无法生长的表型,可被来自高细胞密度tup1Δ培养物的培养滤液挽救,并且该培养滤液中的活性分子被鉴定为一种由11个氨基酸组成的寡肽。使用该肽的合成版本对缺失相应基因的菌株进行活性测定,证明该寡肽作为一种自调节分子,负责密度依赖性表型。尽管在几种子囊菌中已报道了密度依赖性生长表型,但在真菌界尚未有肽作为自调节因子发挥作用的报道。在新型隐球菌中鉴定出一种11聚体肽作为自调节分子,表明真菌界存在多种细胞间通讯机制。

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