Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum

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Kainulainen , V , Von Schantz-Fant , C , Kovanen , R-M , Potdar , S , Laamanen , K , Saarela , J & Satokari , R 2022 , ' Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum ' , npj Biofilms and Microbiomes , vol. 8 , no. 1 , 50 . https://doi.org/10.1038/s41522-022-00312-0

Title: Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum
Author: Kainulainen, Veera; Von Schantz-Fant, Carina; Kovanen, Ruusu-Maria; Potdar, Swapnil; Laamanen, Karoliina; Saarela, Jani; Satokari, Reetta
Contributor organization: Research Programs Unit
HUMI - Human Microbiome Research
University of Helsinki
Institute for Molecular Medicine Finland
Reetta Maria Satokari / Principal Investigator
Date: 2022-06-29
Language: eng
Number of pages: 9
Belongs to series: npj Biofilms and Microbiomes
ISSN: 2055-5008
DOI: https://doi.org/10.1038/s41522-022-00312-0
URI: http://hdl.handle.net/10138/346380
Abstract: Bifidobacterium spp. are abundant gut commensals, especially in breast-fed infants. Bifidobacteria are associated with many health-promoting effects including maintenance of epithelial barrier and integrity as well as immunomodulation. However, the protective mechanisms of bifidobacteria on intestinal epithelium at molecular level are poorly understood. In this study, we developed a high-throughput in vitro screening assay to explore binding receptors of intestinal epithelial cells for Bifidobacterium bifidum. Short interfering RNAs (siRNA) were used to silence expression of each gene in the Caco-2 cell line one by one. The screen yielded four cell surface proteins, SERPINB3, LGICZ1, PKD1 and PAQR6, which were identified as potential receptors as the siRNA knock-down of their expression decreased adhesion of B. bifidum to the cell line repeatedly during the three rounds of siRNA screening. Furthermore, blocking of these host cell proteins by specific antibodies decreased the binding of B. bifidum significantly to Caco-2 and HT29 cell lines. All these molecules are located on the surface of epithelial cells and three out of four, SERPINB3, PKD1 and PAQR6, are involved in the regulation of cellular processes related to proliferation, differentiation and apoptosis as well as inflammation and immunity. Our results provide leads to the first steps in the mechanistic cascade of B. bifidum-host interactions leading to regulatory effects in the epithelium and may partly explain how this commensal bacterium is able to promote intestinal homeostasis.
Subject: GATED ION-CHANNEL
INTESTINAL MICROBIOTA
MOONLIGHTING PROTEINS
ADHESION
PILI
HEALTH
CELLS
318 Medical biotechnology
11832 Microbiology and virology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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