Dairy Propionibacteria: Versatile Probiotics

Members of the genus Bifidobacterium are among the first microbes to colonize the human gastrointestinal tract and are believed to exert positive health benefits on their host. Due to their purported health-promoting properties, bifidobacteria have been incorporated into many functional foods as active ingredients. Bifidobacteria naturally occur in a range of ecological niches that are either directly or indirectly connected to the animal gastrointestinal tract, such as the human oral cavity, the insect gut and sewage. To be able to survive in these particular ecological niches, bifidobacteria must possess specific adaptations to be competitive. Determination of genome sequences has revealed genetic attributes that may explain bifidobacterial ecological fitness, such as metabolic abilities, evasion of the host adaptive immune system and colonization of the host through specific appendages. However, genetic modification is crucial toward fully elucidating the mechanisms by which bifidobacteria exert their adaptive abilities and beneficial properties. In this review we provide an up to date summary of the general features of bifidobacteria, whilst paying particular attention to the metabolic abilities of this species. We also describe methods that have allowed successful genetic manipulation of bifidobacteria.

Dendritic cells (DCs) are antigen-presenting cells that play an essential role in mucosal tolerance. They regularly encounter beneficial intestinal bacteria, but the nature of these cellular contacts and the immune responses elicited by the bacteria are not entirely elucidated. Here, we examined the interactions of Lactobacillus acidophilus NCFM and its cell surface compounds with DCs. L. acidophilus NCFM attached to DCs and induced a concentration-dependent production of IL-10, and low IL-12p70. We further demonstrated that the bacterium binds to DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a DC- specific receptor. To identify the DC-SIGN ligand present on the bacterium, we took advantage of a generated array of L. acidophilus NCFM mutants. A knockout mutant of L. acidophilus NCFM lacking the surface (S) layer A protein (SlpA) was significantly reduced in binding to DC-SIGN. This mutant incurred a chromosomal inversion leading to dominant expression of a second S layer protein, SlpB. In the SlpB-dominant strain, the nature of the interaction of this bacterium with DCs changed dramatically. Higher concentrations of proinflammatory cytokines such as IL-12p70, TNFalpha, and IL-1beta were produced by DCs interacting with the SlpB-dominant strain compared with the parent NCFM strain. Unlike the SlpA-knockout mutant, T cells primed with L. acidophilus NCFM stimulated DCs produced more IL-4. The SlpA-DC-SIGN interaction was further confirmed as purified SlpA protein ligated directly to the DC-SIGN. In conclusion, the major S layer protein, SlpA, of L. acidophilus NCFM is the first probiotic bacterial DC-SIGN ligand identified that is functionally involved in the modulation of DCs and T cells functions.

The outer surface of many archaea and bacteria is coated with a proteinaceous surface layer (known as an S-layer), which is formed by the self-assembly of monomeric proteins into a regularly spaced, two-dimensional array. Bacteria possess dedicated pathways for the secretion and anchoring of the S-layer to the cell wall, and some Gram-positive species have large S-layer-associated gene families. S-layers have important roles in growth and survival, and their many functions include the maintenance of cell integrity, enzyme display and, in pathogens and commensals, interaction with the host and its immune system. In this Review, we discuss our current knowledge of S-layer and related proteins, including their structures, mechanisms of secretion and anchoring and their diverse functions.