Moleculaire en functionele analyses van lectines in Lactobacillus rhamnosus

Probiotics are “live microorganisms, which, when administrated in adequate amounts, confer health benefit on the host” (WHO/FAO 2001). Probiotics are mainly applied in the gastrointestinal tract, but they also have a potential for other niches in the human body such as in the vaginal niche, where lactobacilli are dominant species. Currently, there is a needfor a better molecular understanding of the important properties of probiotics. Therefore, this PhD research was focused on specific molecular and functional characteristics of lactobacilli, to provide general knowledge on the interesting properties for vaginal (versus intestinal) applications, as well as on molecular interaction mechanisms between lactobacilli and HIV. In order to identify genetic mechanisms underlying adaptation to the gastrointestinal and vaginal niche, the well-documented urogenital probiotic strain Lactobacillus rhamnosus GR-1 was genotypically and phenotypically compared with the model gastrointestinal probiotic L. rhamnosus GG. This revealed novel insights in factors that are more relevant for vagina, such as factors for resistance to high concentrations of oxidative stress, and for utilisation and degradation of keratin and heparin. On the other hand, acid resistance and adhesion seem to be important in the gastro-intestinal tract to respectivelywithstand the acid in the stomach and flow in the gut during peristalsis. In addition, we studied the role of endogenous lectins from the modelvaginal L. rhamnosus GR-1 and gastro-intestinal probiotic L. rhamnosus GG by the construction of dedicated knock-out mutants. We were able to show that lectin-like proteins from these probioticstrains are involved in adhesion of the strains to several epithelial cells. A possible role for Llp1 in tissue tropism of L. rhamnosus GR-1 towards vaginal epithelial cells, and not intestinal epithelialcells, was proposed. Finally, we investigated the interaction between our model probiotic strains and HIV, since both the intestine and the vagina niche are reported to be important entry sites for HIV. It has yet been reported that specific Lactobacillus strains show activity against HIV, but the underlying molecular mechanisms were not yet explored. Preliminary data from this PhD work could show that lectins from L. rhamnosus species might play a role in the competitive binding of the virus, but this should be further investigated.status: publishe