The Complete Genome Sequence of the Infant Symbiont Bifidobacterium infantis Reveals Adaptation for Milk Utilization

The bifidobacteria are early colonizers of the breast-fed infant colon and subsequently dominate the lower gastrointestinal tract (GIT) prior to weaning. Accordingly, the infant-isolated Bifidobacterium infantis UCD272 has been shown to utilize human milk oligosaccharides (HMO) as a sole carbon source. This atypical growth is potentially facilitated by observed fucosidase and sialidase activities, which are unknown in the currently sequenced bifidobacteria. Vigorous growth on HMO, as well as the enzymatic activities that contribute to this, has prompted the sequencing of the UCD272 genome to study the genetic basis of this interesting phenotype. UCD272 represents the largest bifidobacterial genome reported to date (2.8 Mbp), and is predicted to contain >500 additional ORFs compared to previously sequenced genomes. Accordingly, the UCD272 genome exhibits an increase in two-component regulatory systems, transport proteins, mobile elements, as well as metabolism-related genes. Furthermore, the B. infantis UCD272 genome sequence possesses a discernable bias towards COGs predicted to utilize mammalian-derived carbohydrates. Many of these genomic features are located in a novel 40-kb gene cluster including the four glycosyl hydrolases that are required to process the milk oligomer in addition to high-affinity oligosaccharide binding proteins and permeases. In an effort to determine the extent to which milk has influenced the evolution of B. infantis as a species, the genomes of additional strains were sequenced to characterize the B. infantis pan-genome. This study significantly advances our understanding of the previously underexplored tripartite coevolution of milk, infants, and their GIT commensals.