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新型抗生物膜化疗药物靶向谷氨酸和谷氨酰胺中的氮。

Novel antibiofilm chemotherapies target nitrogen from glutamate and glutamine.

机构信息

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.

出版信息

Sci Rep. 2018 May 8;8(1):7097. doi: 10.1038/s41598-018-25401-z.

DOI:10.1038/s41598-018-25401-z
PMID:29740028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5940852/
Abstract

Bacteria in nature often reside in differentiated communities termed biofilms, which are an active interphase between uni-cellular and multicellular life states for bacteria. Here we demonstrate that the development of B. subtilis biofilms is dependent on the use of glutamine or glutamate as a nitrogen source. We show a differential metabolic requirement within the biofilm; while glutamine is necessary for the dividing cells at the edges, the inner cell mass utilizes lactic acid. Our results indicate that biofilm cells preserve a short-term memory of glutamate metabolism. Finally, we establish that drugs that target glutamine and glutamate utilization restrict biofilm development. Overall, our work reveals a spatial regulation of nitrogen and carbon metabolism within the biofilm, which contributes to the fitness of bacterial complex communities. This acquired metabolic division of labor within biofilm can serve as a target for novel anti-biofilm chemotherapies.

摘要

自然界中的细菌通常存在于被称为生物膜的分化群落中,生物膜是细菌单细胞和多细胞生命状态之间的活跃中间相。在这里,我们证明枯草芽孢杆菌生物膜的发育依赖于谷氨酰胺或谷氨酸作为氮源。我们在生物膜内显示出不同的代谢需求;虽然谷氨酰胺是边缘分裂细胞所必需的,但内细胞团利用乳酸。我们的结果表明,生物膜细胞保留了对谷氨酸代谢的短期记忆。最后,我们确定靶向谷氨酰胺和谷氨酸利用的药物会限制生物膜的发育。总的来说,我们的工作揭示了生物膜内氮和碳代谢的空间调节,这有助于细菌复杂群落的适应性。这种在生物膜内获得的代谢分工可以作为新型抗生物膜化学疗法的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/4f63a544049a/41598_2018_25401_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/ef683c03007c/41598_2018_25401_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/24f211421edc/41598_2018_25401_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/9a6ee367ea8a/41598_2018_25401_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/f433104021a4/41598_2018_25401_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/4f63a544049a/41598_2018_25401_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/ef683c03007c/41598_2018_25401_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/24f211421edc/41598_2018_25401_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/9a6ee367ea8a/41598_2018_25401_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/f433104021a4/41598_2018_25401_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/5940852/4f63a544049a/41598_2018_25401_Fig5_HTML.jpg

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