Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonization

Abstract Faecalibacterium prausnitzii, a dominant member of healthy human gut microbiota, exhibits a strong positive correlation with fecal fructose levels, suggesting fructose as a key energy source for its colonization and persistence. This study explores the regulatory mechanisms governing the fr...

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Main Authors: HyeLim Choi, Sang-Hyun Cho, Joo-Hong Park, Yeong-Jae Seok
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07878-3
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author HyeLim Choi
Sang-Hyun Cho
Joo-Hong Park
Yeong-Jae Seok
author_facet HyeLim Choi
Sang-Hyun Cho
Joo-Hong Park
Yeong-Jae Seok
author_sort HyeLim Choi
collection DOAJ
description Abstract Faecalibacterium prausnitzii, a dominant member of healthy human gut microbiota, exhibits a strong positive correlation with fecal fructose levels, suggesting fructose as a key energy source for its colonization and persistence. This study explores the regulatory mechanisms governing the fru operon in F. prausnitzii, responsible for fructose uptake and metabolism. Here, we demonstrate that FruR, a DeoR family transcriptional regulator, orchestrates fru operon expression through interactions with fructose-1-phosphate (F1P) and HPr2, the histidine-containing phosphocarrier protein. The F1P-HPr2(Ser-P)-FruR complex enhances RNA polymerase binding to the fru promoter, with stronger affinity for specific operator motifs compared to apo-FruR. F1P induces structural modifications in FruR that strengthen its interaction with HPr2 and alter its DNA recognition pattern, facilitating RNA polymerase access to the promoter. In vivo experiments in mice demonstrate increased F. prausnitzii abundance alongside upregulated fru operon expression in fructose-rich environments. This study provides new insights into how fructose availability modulates fru operon regulation and promotes F. prausnitzii colonization in the host intestine.
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spelling doaj-art-ee24e8cfe41443e8a4db6565ee41906f2025-08-20T03:01:45ZengNature PortfolioCommunications Biology2399-36422025-03-018111210.1038/s42003-025-07878-3Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonizationHyeLim Choi0Sang-Hyun Cho1Joo-Hong Park2Yeong-Jae Seok3School of Biological Sciences, Seoul National UniversitySchool of Biological Sciences, Seoul National UniversitySchool of Biological Sciences, Seoul National UniversitySchool of Biological Sciences, Seoul National UniversityAbstract Faecalibacterium prausnitzii, a dominant member of healthy human gut microbiota, exhibits a strong positive correlation with fecal fructose levels, suggesting fructose as a key energy source for its colonization and persistence. This study explores the regulatory mechanisms governing the fru operon in F. prausnitzii, responsible for fructose uptake and metabolism. Here, we demonstrate that FruR, a DeoR family transcriptional regulator, orchestrates fru operon expression through interactions with fructose-1-phosphate (F1P) and HPr2, the histidine-containing phosphocarrier protein. The F1P-HPr2(Ser-P)-FruR complex enhances RNA polymerase binding to the fru promoter, with stronger affinity for specific operator motifs compared to apo-FruR. F1P induces structural modifications in FruR that strengthen its interaction with HPr2 and alter its DNA recognition pattern, facilitating RNA polymerase access to the promoter. In vivo experiments in mice demonstrate increased F. prausnitzii abundance alongside upregulated fru operon expression in fructose-rich environments. This study provides new insights into how fructose availability modulates fru operon regulation and promotes F. prausnitzii colonization in the host intestine.https://doi.org/10.1038/s42003-025-07878-3
spellingShingle HyeLim Choi
Sang-Hyun Cho
Joo-Hong Park
Yeong-Jae Seok
Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonization
Communications Biology
title Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonization
title_full Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonization
title_fullStr Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonization
title_full_unstemmed Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonization
title_short Fructose-responsive regulation by FruR in Faecalibacterium prausnitzii for its intestinal colonization
title_sort fructose responsive regulation by frur in faecalibacterium prausnitzii for its intestinal colonization
url https://doi.org/10.1038/s42003-025-07878-3
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