The characterisation of lactobacillus glycoconjugates and their interplay with candida

The role of lactobacillary glycoconjugates in keystone host-microbe and microbe-microbe interactions was explored in this PhD thesis. Lactobacilli occur in a wide variety of ecosystems, ranging from various human niches towards various animals, plants and food-related habitats, where they can have a beneficial role as “keystone taxa”. This keystone role can be conceptualized as immune modulation of the host and antimicrobial effects on surrounding micro-organisms. The molecules conferring these modulatory and antimicrobial activities to Lactobacillus are however still largely unknown. Glycoconjugates are currently underexplored, but their large structural variety and prominent position on the cell wall or in the supernatant make them interesting components to contribute to specific modulatory and antimicrobial effects. In the PhD thesis, first an overview of the Lactobacillus cell wall structures is provided, with a special focus on the already described functionalities of glycoconjugates in relation to microbe-microbe and microbe-host interactions. Next, the genetic abilities to produce exopolysaccharides (EPS) as main glycoconjugates of interest by lactobacilli were systematically explored. This analysis showed that certain EPS characteristics are more species- or phylogroup-specific than strain-specific as generally believed. A few of these more ‘general’ characteristics could be linked to the lifestyle associated with the phylogroups, indicating that certain structural features of EPS are indeed of importance for the role Lactobacillus plays in that specific environment. As a case study, we explored a possible association between EPS structure and lifestyle adaptation for Lactobacillus casei AMBR2, one of the first Lactobacillus isolates from the upper respiratory tract. This EPS structure showed very unique structural properties and a special role in adhesion and cytokine induction by L. casei AMBR2. Subsequently, the functional activity of EPS and glycoproteins from the model gastro-intestinal probiotic strain Lactobacillus rhamnosus GG was explored against Candida albicans as key microbe-microbe interaction of interest for multiple applications. The EPS molecules of L. rhamnosus GG appeared to be indeed, involved in the direct competition of L. rhamnosus GG with C. albicans during epithelial adhesion. However, a more pronounced role was found for the glycoprotein and cell wall hydrolase Msp1 because Msp1 was able to significantly block hyphae formation by this opportunistic pathogen. To translate these observations to an in vivo setting, the effects of L. rhamnosus GG and Msp1 on C. albicans infection in Galleria mellonella larvae was investigated.

Publication year:2019

Keywords:Doctoral thesis

Accessibility:Closed