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商业黏蛋白的铁含量有助于囊性纤维化气道合成微生物群落的组成稳定性。

Iron content of commercial mucin contributes to compositional stability of a cystic fibrosis airway synthetic microbiota community.

作者信息

Giedraitis Emily, Neve Rachel L, Phelan Vanessa V

机构信息

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado - Anschutz Medical Campus, Aurora, CO, 80045, USA.

Department of Immunology and Microbiology, School of Medicine, University of Colorado - Anschutz Medical Campus, Aurora, CO, 80045, USA.

出版信息

bioRxiv. 2024 Sep 6:2024.09.06.611695. doi: 10.1101/2024.09.06.611695.

Abstract

culture models of mucosal environments are used to elucidate the mechanistic roles of the microbiota in human health. These models often include commercial mucins to reflect the role of mucins as an attachment site and nutrient source for the microbiota. Two types of mucins are commercially available: porcine gastric mucin (PGM) and bovine submaxillary mucin (BSM). These commercial mucins have been shown to contain iron, an essential element required by the microbiota as a co-factor for a variety of metabolic functions. In these mucin preparations, the concentration of available iron can exceed physiological concentrations present in the native environment. This unexpected source of iron influences experimental outcomes, including shaping the interactions between co-existing microbes in synthetic microbial communities used to elucidate the multispecies interactions within native microbiota. In this work, we leveraged the well-characterized iron-dependent production of secondary metabolites by the opportunistic pathogen to aid in the development of a simple, low-cost, reproducible workflow to remove iron from commercial mucins. Using the mucosal environment of the cystic fibrosis (CF) airway as a model system, we show that is canonically responsive to iron concentration in the chemically defined synthetic CF medium complemented with semi-purified PGM, and community composition of a clinically relevant, synthetic CF airway microbial community is modulated, in part, by iron concentration in PGM.

摘要

黏膜环境的培养模型用于阐明微生物群在人类健康中的作用机制。这些模型通常包括商业黏蛋白,以反映黏蛋白作为微生物群附着位点和营养源的作用。有两种商业可用的黏蛋白:猪胃黏蛋白(PGM)和牛颌下黏蛋白(BSM)。这些商业黏蛋白已被证明含有铁,铁是微生物群作为多种代谢功能辅助因子所需的必需元素。在这些黏蛋白制剂中,可利用铁的浓度可能超过自然环境中存在的生理浓度。这种意外的铁来源会影响实验结果,包括塑造用于阐明自然微生物群中多物种相互作用的合成微生物群落中共存微生物之间的相互作用。在这项工作中,我们利用机会性病原体对铁依赖性次级代谢产物的充分表征,来协助开发一种简单、低成本、可重复的流程,以从商业黏蛋白中去除铁。以囊性纤维化(CF)气道的黏膜环境作为模型系统,我们表明,在补充了半纯化PGM的化学定义合成CF培养基中,[具体病原体名称未给出]对铁浓度具有典型反应,并且临床相关的合成CF气道微生物群落的组成部分受到PGM中铁浓度的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7823/11398496/f360e97bc922/nihpp-2024.09.06.611695v1-f0001.jpg

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