Evaluation of the molecular cross-talk between bifidobacteria and the human host

The human being is considered a complex biological system, the holobiont, which harbors a wide range of symbiotic microorganisms. The heterogenous and intricated community of bacteria colonizing the intestinal environment is called gut microbiota. This microbial community has an important impact on the host health and an intense cross-talk between the two entities is established. Substantial scientific interest has been focused on the molecular mechanisms which drive the interactions between the microbiota and the host, focusing especially on the adhesion and persistence properties of bifidobacteria in colonizing the human gut. In fact, bifidobacteria are key model organisms for the investigation of the molecular mechanisms underlying the microbial interactions occurring in the human gut. This Ph.D. thesis aims to study and deepen the mechanisms leading bifidobacteria, specifically Bifidobacterium bifidum PRL2010, to interact with the human host. Specifically, the molecular characterization of specific genes involved in such functions was investigated. In particular, the first section of this Ph.D. thesis focuses on the investigation of bifidobacterial ability to utilize a specific host glycan to colonize the intestinal environment and persist in this complex and competitive niche. Therefore, the mechanisms involved in long-term persistence and competitivity are examined. The second section of the thesis investigates specific extracellular structures, teichoic acids, whose exact function in bifidobacteria has been poorly studied. In particular, the inter- and intra-species transcriptional profile of teichoic acid encoding genes has been investigated and the immunomodulatory role and intestinal adhesion abilities have been deepened. Finally, novel notions on the molecular mechanisms regulating quorum sensing, i.e. a cell-density system modulated by a signaling molecule called autoinducer, have been acquired. Specifically, the involvement of the autoinducer in bifidobacterial metabolism, stress response and ability to establish a cross-talk with the host has been examined. In particular the influence of such molecule in the adhesion to human intestinal cells and, therefore, the ability to persist in the gut environment have been investigated in this PhD thesis.