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从鸽粪中嘌呤的定量分析及其对新型隐球菌感染期间存活的影响。

Quantitation of Purines from Pigeon Guano and Implications for Cryptococcus neoformans Survival During Infection.

机构信息

Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, 4072, Australia.

Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.

出版信息

Mycopathologia. 2019 Apr;184(2):273-281. doi: 10.1007/s11046-018-0315-0. Epub 2019 Feb 1.

DOI:10.1007/s11046-018-0315-0
PMID:30707338
Abstract

The fertilizing properties of bird manure, or guano, have played an important role in plant cultivation for thousands of years. Research into its chemical composition by Unger in 1846 identified a novel compound, now known as guanine, a purine base that is essential for DNA and RNA biosynthesis and cell signalling. Nitrogen-rich guano can also harbour human pathogens, one significant example being the fungal pathogen Cryptococcus neoformans. Historically associated with pigeon droppings, C. neoformans is able to infect immunocompromised individuals with the aid of a number of adaptive virulence traits. To gain insight into this niche, a quantitative analysis of pigeon guano was performed by LC/MS to determine the concentrations of purines present. Guanine was found in abundance, in particular, in aged guano samples that contained 156-296 μg/g [w/w] compared to 75 μg/g in fresh guano. Adenine concentrations were more consistent between fresh and aged samples, 13 μg/g compared to 10-15 μg/g, respectively. C. neoformans strains that lack key enzymes of the de novo purine synthesis pathway and are guanine or adenine auxotrophs displayed differences in their ability to exploit this substrate: growth of a guanine auxotrophic mutant (gua1Δ) was partially restored on 30% pigeon guano media, but an adenine auxotrophic mutant (ade13Δ) was unable to grow. We conclude that while purine salvage is likely a useful resource-saving mechanism, alone it is not sufficient to fully provide the purines required by wild-type C. neoformans growing in its guano niche.

摘要

鸟粪(即鸟粪)的受精特性在几千年来对植物栽培起着重要作用。1846 年,Unger 对其化学组成的研究鉴定出一种新型化合物,即现在已知的鸟嘌呤,它是 DNA 和 RNA 生物合成和细胞信号所必需的嘌呤碱基。富含氮的鸟粪还可能携带人类病原体,其中一个重要的例子是真菌病原体新生隐球菌。新生隐球菌历史上与鸽子粪便有关,在许多适应性毒力特征的帮助下,它能够感染免疫功能低下的个体。为了深入了解这个生态位,通过 LC/MS 对鸽子粪便进行了定量分析,以确定存在的嘌呤浓度。鸟嘌呤含量丰富,特别是在含有 156-296μg/g[w/w]的陈旧鸟粪样本中,而新鲜鸟粪中鸟嘌呤含量为 75μg/g。腺嘌呤浓度在新鲜和陈旧样本之间更为一致,分别为 13μg/g 和 10-15μg/g。缺乏从头嘌呤合成途径关键酶且为鸟嘌呤或腺嘌呤营养缺陷型的新生隐球菌菌株在利用这种底物的能力上存在差异:鸟嘌呤营养缺陷型突变体(gua1Δ)在 30%的鸽子粪便培养基上的生长部分得到恢复,但腺嘌呤营养缺陷型突变体(ade13Δ)无法生长。我们得出结论,虽然嘌呤回收可能是一种有用的资源节约机制,但它本身不足以完全提供在其鸟粪生态位中生长的野生型新生隐球菌所需的嘌呤。

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