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皮肤丙酸杆菌中的卟啉生成与调控。

Porphyrin Production and Regulation in Cutaneous Propionibacteria.

机构信息

Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.

Northern Ireland Centre for Stratified Medicine, Ulster University, Londonderry, United Kingdom.

出版信息

mSphere. 2020 Jan 15;5(1):e00793-19. doi: 10.1128/mSphere.00793-19.

Abstract

Porphyrins are intermediate metabolites in the biosynthesis of vital molecules, including heme, cobalamin, and chlorophyll. Bacterial porphyrins are known to be proinflammatory, with high levels linked to inflammatory skin diseases. species are dominant skin commensals and play essential roles in defending against pathogens and in triggering an inflammatory response. To better understand how the inflammatory potential of the skin microbiome may vary depending on its propionibacterial composition, we compared the production levels of porphyrins among , , , and strains. We found that porphyrin production varied among these species, with type I strains producing significantly larger amounts of porphyrins than type II and III strains and other species. strains that are highly associated with the common skin condition acne vulgaris responded to vitamin B supplementation with significantly higher porphyrin production. In contrast, vitamin B supplementation had no effect on the porphyrin production of health-associated strains and other propionibacteria. We observed low-level porphyrin production in most strains harboring the repressor gene, with the exception of strains belonging to type I clades IB-3 and IC. Our findings shed light on the proinflammatory potential of distinct phylogenetic lineages of as well as other resident skin propionibacteria. We demonstrate that the overall species and strain composition is important in determining the metabolic output of the skin microbiome in health and disease. Porphyrins are a group of metabolites essential to the biosynthesis of heme, cobalamin, and chlorophyll in living organisms. Bacterial porphyrins can be proinflammatory, with high levels linked to human inflammatory diseases, including the common skin condition acne vulgaris. Propionibacteria are among the most abundant skin bacteria. Variations in propionibacteria composition on the skin may lead to different porphyrin levels and inflammatory potentials. This study characterized porphyrin production in all lineages of , the most dominant skin , and other resident skin propionibacteria, including , , and We revealed that type I strains produced significantly more porphyrins than did type II and III strains and other species. The findings from this study shed light on the proinflammatory potential of the skin microbiome and can be used to guide the development of effective acne treatments by modulating the skin microbiome and its metabolic activities.

摘要

卟啉是生物合成重要分子(包括血红素、钴胺素和叶绿素)的中间代谢物。已知细菌卟啉具有促炎作用,高水平的卟啉与炎症性皮肤病有关。丙酸杆菌是主要的皮肤共生菌,在抵御病原体和引发炎症反应方面发挥着重要作用。为了更好地了解皮肤微生物组的炎症潜力可能因其丙酸杆菌组成而有所不同,我们比较了 、 、 、和 菌株的卟啉产生水平。我们发现这些物种的卟啉产生水平不同,I 型菌株产生的卟啉明显多于 II 型和 III 型菌株和其他 物种。与常见皮肤病痤疮高度相关的菌株对维生素 B 补充的卟啉产生反应明显更高。相比之下,维生素 B 补充对健康相关的 菌株和其他丙酸杆菌的卟啉产生没有影响。我们观察到大多数携带 抑制基因的 菌株产生低水平的卟啉,除了属于 I 型 clade IB-3 和 IC 的 菌株。我们的研究结果揭示了不同进化谱系的 以及其他常驻皮肤丙酸杆菌的促炎潜力。我们证明,总体物种和菌株组成对于确定健康和疾病状态下皮肤微生物组的代谢产物输出非常重要。卟啉是生物体内血红素、钴胺素和叶绿素生物合成所必需的一组代谢物。细菌卟啉可能具有促炎作用,高水平的卟啉与人类炎症性疾病有关,包括常见的皮肤病痤疮。丙酸杆菌是最丰富的皮肤细菌之一。皮肤上丙酸杆菌组成的变化可能导致卟啉水平和炎症潜力的不同。本研究对所有 谱系、最主要的皮肤共生菌 以及其他常驻皮肤丙酸杆菌(包括 、 、和 )的卟啉产生进行了表征。我们发现 I 型菌株产生的卟啉明显多于 II 型和 III 型菌株和其他 物种。本研究的结果揭示了皮肤微生物组的促炎潜力,并可通过调节皮肤微生物组及其代谢活性来指导有效的痤疮治疗方法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4326/6968654/be21bfb447d8/mSphere.00793-19-f0001.jpg

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