Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum.
Veera KainulainenCarina von Schantz-FantRuusu-Maria KovanenSwapnil PotdarKaroliina LaamanenJani SaarelaSatokari ReettaPublished in: NPJ biofilms and microbiomes (2022)
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.
Keyphrases
- high throughput
- genome wide
- cancer therapy
- poor prognosis
- binding protein
- cell surface
- oxidative stress
- single cell
- endothelial cells
- public health
- dna methylation
- mental health
- dna binding
- copy number
- signaling pathway
- transcription factor
- polycystic kidney disease
- stem cells
- drug delivery
- cell death
- endoplasmic reticulum stress
- gene expression
- escherichia coli
- mesenchymal stem cells
- climate change
- cystic fibrosis
- drug induced