Bifidobacterium breve UCC2003 Employs Multiple Transcriptional Regulators To Control Metabolism of Particular Human Milk Oligosaccharides

• Published in: Applied and environmental microbiology Vol. 84; no. 9; p. e02774-17
• Main Authors: James, Kieran, O'Connell Motherway, Mary, Penno, Christophe, O'Brien, Rebecca Louise, van Sinderen, Douwe
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.05.2018
• Subjects: Allosteric properties; Bifidobacterium breve; Bifidobacterium breve - genetics; Breast Feeding; Breast milk; Carbohydrate metabolism; Carbohydrates; Gene Expression Regulation, Bacterial; Gene loci; Gene sequencing; Humans; Infant; Infant, Newborn; Metabolic Networks and Pathways; Metabolic pathways; Metabolism; Microbiota; Milk, Human - microbiology; Monosaccharides; Oligosaccharides; Oligosaccharides - metabolism; Physiology; Polysaccharides; Prebiotics; Probiotics; Regulators; Regulatory Elements, Transcriptional - genetics; Regulatory mechanisms (biology); Spotlight; Transcription; bifidobacteria; probiotic; HMO; prebiotic; carbohydrate metabolism; transcriptional regulation
• ISSN: 0099-2240; 1098-5336
• DOI: 10.1128/aem.02774-17

Bifidobacterial carbohydrate metabolism has been studied in considerable detail for a variety of both plant- and human-derived glycans, particularly involving the bifidobacterial prototype strain UCC2003. We recently elucidated the metabolic pathways by which the uman ilk ligosaccharide (HMO) constituents lacto- -tetraose (LNT), lacto- -neotetraose (LNnT) and lacto- -biose (LNB) are utilized by UCC2003. However, to date, no work has been carried out on the regulatory mechanisms that control the expression of the genetic loci involved in these HMO metabolic pathways. In this study, we describe the characterization of three transcriptional regulators and the corresponding operator and associated (inducible) promoter sequences, with the latter governing the 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. 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, to date there is very little understanding of the transcriptional regulation of these pathways. This study reveals a multicomponent transcriptional regulation system that controls the recently identified pathways of HMO metabolism in the infant-associated 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.