A Bifidobacterial pilus-associated protein promotes colonic epithelial proliferation.
Mary O'Connell MotherwayAileen HoustonGrace O'CallaghanJustus ReunanenFrances O'BrienTara O'DriscollPatrick G CaseyWillem M de VosDouwe van SinderenFergus ShanahanPublished in: Molecular microbiology (2018)
Development of the human gut microbiota commences at birth, with certain bifidobacterial species representing dominant and early colonisers of the newborn gastrointestinal tract. The molecular basis of Bifidobacterium colonisation, persistence and presumed communication with the host has remained obscure. We previously identified tight adherence (Tad) pili from Bifidobacterium breve UCC2003 as an essential colonisation factor. Here, we demonstrate that bifidobacterial Tad pili also promote in vivo colonic epithelial proliferation. A significant increase in cell proliferation was detectable 5 days postadministration of B. breve UCC2003. Using advanced functional genomic approaches, bacterial strains either (a) producing the Tad2003 pili or (b) lacking the TadE or TadF pseudopilins were created. Analysis of the ability of these mutant strains to promote epithelial cell proliferation in vivo demonstrated that the pilin subunit, TadE, is the bifidobacterial molecule responsible for this proliferation response. These findings were confirmed in vitro using purified TadE protein. Our data imply that bifidobacterial Tad pili may contribute to the maturation of the naïve gut in early life through the production of a specific scaffold of extracellular protein structures, which stimulate growth of the neonatal mucosa.
Keyphrases
- cell proliferation
- early life
- signaling pathway
- escherichia coli
- cell cycle
- endothelial cells
- pi k akt
- protein protein
- ulcerative colitis
- amino acid
- electronic health record
- type diabetes
- copy number
- adipose tissue
- dna methylation
- metabolic syndrome
- pregnant women
- machine learning
- small molecule
- mass spectrometry
- induced pluripotent stem cells
- genome wide
- deep learning
- artificial intelligence
- protein kinase