A Bifidobacterial pilus‐associated protein promotes colonic epithelial proliferation. Issue 1 (2nd December 2018)

• Record Type: Journal Article
• Authors: O'Connell Motherway, Mary; Houston, Aileen; O'Callaghan, Grace; Reunanen, Justus; O'Brien, Frances; O'Driscoll, Tara; Casey, Patrick G.; de Vos, Willem M.; van Sinderen, Douwe; Shanahan, Fergus
• Is Part Of: Molecular microbiology. Volume 111:Issue 1(2019)
• Page Start: 287
• Page End: 301
• Publication Date: 2018-12-02
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14155
• Languages: English
• ISSNs: 0950-382X

Abstract

Abstract: 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. Abstract : Bifidobacteria are among the first colonisers of the newborn gastrointestinal tract, and appreciated to positively impact on host health. Previously, we identified bifidobacterial Tad pili as an essential and conserved colonisation factor. Here, we show that Tad pili, and specifically a pseudopilin subunit, TadE, are involved in host signalling, leading to in vivo colonic epithelial proliferation. These findings could have several therapeutic implications, particularly in the management of preterm babies with suboptimal mucosal maturation.