Bifidobacteria are common inhabitants of the human gastrointestinal tract that, despite a long history of research, have not shown any pathogenic potential whatsoever. By contrast, some bifidobacteria are associated with a number of health-related benefits for the host. The reported beneficial effects of bifidobacteria include competitive exclusion of pathogens, alleviation of symptoms of irritable bowel syndrome and inflammatory bowel disease, and modulation of intestinal and systemic immune responses. Based on these effects, bifidobacteria are widely used as probiotics by pharmaceutical and dairy industries. In order to exert a beneficial effect bifidobacteria have to, at least transiently, colonize the host in a sufficient population size. Besides other criteria such as resistance to manufacturing processes and intestinal transit, potential probiotic bacteria are tested for adhesion to the host structures including intestinal epithelial cells, mucus, and extracellular matrix components. In the present review article, we summarize the current knowledge on bifidobacterial structures that mediate adhesion to host tissue and compare these to similar structures of pathogenic bacteria. This reveals that most of the adhesive structures and mechanisms involved in adhesion of bifidobacteria to host tissue are similar or even identical to those employed by pathogens to cause disease. It is thus reasonable to assume that these structures and mechanisms are equally important for commensal or probiotic bacteria and play a similar role in the beneficial effects exerted by bifidobacteria.

Bifidobacteria are one of the predominant bacterial groups of the human intestinal microbiota and have important functional properties making them interesting for the food and dairy industries. Numerous in vitro and preclinical studies have shown beneficial effects of particular bifidobacterial strains or strain combinations on various health parameters of their hosts. This indicates the potential of bifidobacteria in alternative or supplementary therapeutic approaches in a number of diseased states. Based on these observations, bifidobacteria have attracted considerable interest by the food, dairy, and pharmaceutical industries and they are widely used as so-called probiotics. As a consequence of the rapidly increasing number of available bifidobacterial genome sequences and their analysis, there has been substantial progress in the identification of bifidobacterial structures involved in colonisation of and interaction with the host. With the present review, we aim to provide an update on the current knowledge on the mechanisms by which bifidobacteria colonise their hosts and exert health promoting effects.

Health-promoting effects have been attributed to a number of Bifidobacterium sp. strains. These effects as well as the ability to colonise the host depend on secreted proteins. Moreover, rational design of protein secretion systems bears the potential for the generation of novel probiotic bifidobacteria with improved health-promoting or therapeutic properties. To date, there is only very limited data on secretion signals of bifidobacteria available. Using in silico analysis, we demonstrate that all bifidobacteria encode the major components of Sec-dependent secretion machineries but only B. longum strains harbour Tat protein translocation systems. A reporter plasmid for secretion signals in bifidobacteria was established by fusing the coding sequence of the signal peptide of a sialidase of Bifidobacterium bifidum S17 to the phytase gene appA of E. coli. The recombinant strain showed increased phytase activity in spent culture supernatants and reduced phytase levels in crude extracts compared to the control indicating efficient phytase secretion. The reporter plasmid was used to screen seven predicted signal peptides in B. bifidum S17 and B. longum E18. The tested signal peptides differed substantially in their efficacy to mediate protein secretion in different host strains. An efficient signal peptide was used for expression and secretion of a therapeutically relevant protein in B. bifidum S17. Expression of a secreted cytosine deaminase led to a 100-fold reduced sensitivity of B. bifidum S17 to 5-fluorocytosine compared to the non-secreted cytosine deaminase suggesting efficient conversion of 5-fluorocytosine to the cytotoxic cancer drug 5-fluorouracil by cytosine deaminase occurred outside the bacterial cell. Selection of appropriate signal peptides for defined protein secretion might improve therapeutic efficacy as well as probiotic properties of bifidobacteria.

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Here, we report on the first completely annotated genome sequence of a Bifidobacterium bifidum strain. B. bifidum S17, isolated from feces of a breast-fed infant, was shown to strongly adhere to intestinal epithelial cells and has potent anti-inflammatory activity in vitro and in vivo. The genome sequence will provide new insights into the biology of this potential probiotic organism and allow for the characterization of the molecular mechanisms underlying its beneficial properties.Bifidobacteria represent an important group of the intestinal microbiota of humans and are believed to be promising candidates for pharmaceutical applications and functional food products due to their ability to exclude intestinal pathogens, strengthen the intestinal barrier, and/or modulate the immune response in the intestine (8). In order to unravel the molecular mechanisms responsible for these beneficial effects, several bifidobacterial strains have recently been sequenced (17). However, while the genus Bifidobacterium comprises 31 species with nine subspecies, at present only nine whole-genome sequences of four species and two subspecies are publically available (9).Here, we present the first fully annotated genome sequence for the species Bifidobacterium bifidum. The strain selected for sequencing (B. bifidum S17) was isolated from feces of a breast-fed infant. B. bifidum S17 was shown to display unusually strong adhesion to intestinal epithelial cells (IECs) (11,12) and elicits a promising anti-inflammatory capacity both in vitro (11,13) and in vivo in a murine model of colitis (11).A long tag paired-end library was constructed from genomic DNA and sequenced using a Roche Genome Sequencer FLX Titanium by Eurofins MWG Operon (Ebersberg, Germany). A total of 372,681 reads with a total of 75,885,699 bp were obtained, giving 34.7-fold coverage. A total of 321,408 reads were marked as mate pairs. Sequences were assembled by gsAssembler (Roche Applied Science) and Staden (15) into a total of 48 contigs distributed over three scaffolds. Remaining inter-and intrascaffold gaps were closed by Sanger sequencing of PCR products. Potential frameshifts were identified using FSfind (7) and verified by Sanger sequencing. Protein-encoding open reading frames (ORFs) were identified by employing Prodigal (5) using standard settings. The resulting translations were used for a BLASTP (1) search against the nonredundant GenBank database. All automatically annotated ORFs were manually corrected using the Artemis software (14) based on the presence of a potential ribosomal binding sites and alignments with homologous ORFs from other organisms, and the start codons were redefined where necessary. Initial automated functional assignment was done using TIGRFam (3), Pfam (2), and Interpro (4), as well as KEGG (6) and COG (16) predictions. Manual corrections of automatically assigned functions were verified on an individual gene-bygene basis. The pSORT software (http://psort.hgc.jp/) was used to predict protein localization. tRNA genes were identified by ...