Bifidobacterium breve UCC2003 employs multiple transcriptional regulators to control metabolism of particular human milk oligosaccharides

James, Kieran; O'Connell Motherway, Mary; Penno, Christophe; O'Brien, Rebecca L.; van Sinderen, Douwe

Bifidobacterium breve UCC2003 employs multiple transcriptional regulators to control metabolism of particular human milk oligosaccharides

Files

5060.pdf(1.91 MB)

Accepted Version

zam009188498s1.pdf(1.62 MB)

Supplementary Material

Date

2018-03-02

Authors

James, Kieran

O'Connell Motherway, Mary

Penno, Christophe

O'Brien, Rebecca L.

van Sinderen, Douwe

Publisher

American Society for Microbiology

Published Version

10.1128/aem.02774-17

Abstract

Bifidobacterial carbohydrate metabolism has been studied in considerable detail for a variety of both plant and human-derived glycans, particularly involving the bifidobacterial prototype Bifidobacterium breve UCC2003. We recently elucidated the metabolic pathways by which the human milk oligosaccharide (HMO) constituents lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT) and lacto-N-biose (LNB) are utilized by B. breve UCC2003. However, to date no work has been carried out on the regulatory mechanisms that control expression of the genetic loci involved in these HMO metabolic pathways. In the current study, we describe the characterization of three transcriptional regulators and corresponding operator and associated (inducible) promoter sequences, the latter governing transcription of the genetic elements involved in LN(n)T/LNB metabolism. The activity of these regulators is dependent on the release of specific monosaccharides, which are believed to act as allosteric effectors, and which are derived from the corresponding HMOs targeted by the particular locus.Importance Human milk oligosaccharides (HMOs) are a key factor in the development of the breastfed infant microbiota. They function as prebiotics, selecting for a specific range of microbes, including a number of infant-associated species of bifidobacteria, which are thought to provide a range of health benefits to the infant host. While much research has been carried out on elucidating the mechanisms of HMO metabolism in infant-associated bifidobacteria, there is to date very little understanding of the transcriptional regulation of these pathways. The current study reveals a multi-component transcriptional regulation system that controls the recently-identified pathways of HMO metabolism in the infant-associated Bifidobacterium breve prototype strain UCC2003. This not only provides insight into the regulatory mechanisms present in other infant-associated bifidobacteria, but also provides an example of a network of sequential steps regulating microbial carbohydrate metabolism.

Keywords

Bifidobacteria , Probiotic , Prebiotic , Transcriptional regulation , HMO , Carbohydrate metabolism

Citation

James, K., O'Connell Motherway, M., Penno, C., O'Brien, R. L. and van Sinderen, D. (2018) 'Bifidobacterium breve UCC2003 employs multiple transcriptional regulators to control metabolism of particular human milk oligosaccharides', Applied and Environmental Microbiology, 84(9), e02774-17 (21pp). doi:10.1128/aem.02774-17