Dataset Information

BPP43_05035 is a Brachyspira pilosicoli cell surface adhesin that weakens the integrity of the epithelial barrier during infection

ABSTRACT: The anaerobic spirochete Brachyspira causes intestinal spirochetosis, characterized by the intimate attachment of bacterial cells to the colonic mucosa, potentially leading to symptoms such as diarrhea, abdominal pain, and weight loss. Despite the clinical significance of Brachyspira infections, the mechanism of the interaction between Brachyspira and the colon epithelium is not known. We characterized the molecular mechanism of the B. pilosicoli-epithelium interaction and its impact on the epithelial barrier during infection. Through a proteomics approach, we identified BPP43_05035 as a candidate B. pilosicoli surface protein that mediates bacterial attachment to cultured human colonic epithelial cells. The crystal structure of BPP43_05035 revealed a globular lipoprotein with a six-bladed beta-propeller domain. Blocking the native BPP43_05035 on B. pilosicoli, either with a specific antibody or via competitive inhibition, abrogated its binding to epithelial cells, which required cell surface-exposed N-glycans. Proximity labeling and interaction assays revealed that BPP43_05035 bound to tight junctions, thereby increasing the permeability of the epithelial monolayer. Extending our investigation to humans, we discovered a downregulation of tight junction and brush border genes in B. pilosicoli-infected patients carrying detectable levels of epithelium-bound BPP43_05035. Collectively, our findings identify BPP43_05035 as a B. pilosicoli adhesin that weakens the colonic epithelial barrier during infection.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Brachyspira Pilosicoli P43/6/78

TISSUE(S): Colon

SUBMITTER: Johannes Fuchs

LAB HEAD: Thaher Pelaseyed

PROVIDER: PXD056942 | Pride | 2024-10-18

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	4740_TMTpro_UP10793_SPhuman_2miss_Lumos_230911_FAIMS_14to43.msf	Msf
	4740_TMTpro_UP10793_SPhuman_2miss_Lumos_230911_FAIMS_14to43.pdResult	Other
	Lumos_230911_FAIMS_14.raw	Raw
	Lumos_230911_FAIMS_15.raw	Raw
	Lumos_230911_FAIMS_16.raw	Raw

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BPP43_05035 is a Brachyspira pilosicoli cell surface adhesin that weakens the integrity of the epithelial barrier during infection.

Rajan Anandi A Gallego Pablo P Dolan Brendan B Patel Piyush P Dwibedi Chinmay C Luis Ana S AS Trillo-Muyo Sergio S Arike Liisa L van der Post Sjoerd S Simrén Magnus M Pelaseyed Thaher T

Gut microbes 20240101 1

The anaerobic spirochete Brachyspira causes intestinal spirochetosis, characterized by the intimate attachment of bacterial cells to the colonic mucosa, potentially leading to symptoms such as diarrhea, abdominal pain, and weight loss. Despite the clinical significance of Brachyspira infections, the mechanism of the interaction between Brachyspira and the colon epithelium is not known. We characterized the molecular mechanism of the B. pilosicoli-epithelium interactio ...[more]

PMID: 39349383

Publication: 1/2

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Project description:The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. Transcriptome analysis revealed a global down-regulation of physiological AJC gene expression in the SAE of healthy smokers (n=53) compared to healthy nonsmokers (n=59), an observation associated with changes in molecular pathways regulating epithelial differentiation such as PTEN signaling and accompanied by induction of cancer-related AJC genes. Genome-wide co-expression analysis identified a smoking-sensitive AJC transcriptional network. The overall expression of AJC-associated genes was further decreased in COPD smokers (n=23). Exposure of human airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC-related genes, accompanied by decreased transepithelial resistance. Thus, cigarette smoking alters the AJC gene expression architecture in the human airway epithelium, providing a molecular basis for the dysregulation of airway epithelial barrier function during the development of smoking-induced lung disease. The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. In this study, microarray analysis of the SAE obtained from 53 healthy nonsmokers, 59 healthy smokers, and 23 smokers with COPD was performed to determine physiological AJC gene expression architecture in the SAE and its modification by cigarette smoking and during the development of COPD.

Dataset Information

BPP43_05035 is a Brachyspira pilosicoli cell surface adhesin that weakens the integrity of the epithelial barrier during infection

Dataset's files

Publications

BPP43_05035 is a <i>Brachyspira pilosicoli</i> cell surface adhesin that weakens the integrity of the epithelial barrier during infection.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

BPP43_05035 is a Brachyspira pilosicoli cell surface adhesin that weakens the integrity of the epithelial barrier during infection

Dataset's files

Publications

BPP43_05035 is a &lt;i&gt;Brachyspira pilosicoli&lt;/i&gt; cell surface adhesin that weakens the integrity of the epithelial barrier during infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

BPP43_05035 is a <i>Brachyspira pilosicoli</i> cell surface adhesin that weakens the integrity of the epithelial barrier during infection.