Structural basis of probiotic LGG adhesion to the gut

Frequent and inappropriate use of antibiotics leads to the development of resistance and removal of the gut microbiota, which are critical for our survival. Hence, the search for alternative approaches, including the use of probiotics, is being explored. Consuming probiotics provides various health-promoting effects like preventing harmful microbes that can cause infection. One of the vital criteria in choosing bacteria to be a probiotic is, it must have the ability to attach and persist in the human gut since adhesion and subsequent colonization is a prerequisite for providing beneficial effects. Lactobacillus rhamnosus GG (LGG) is one of the widely used probiotic strains for its various beneficial effects and excellent survival in the gut. Hair-like surface organelle called pili or fimbriae in LGG is a major contributing factor for its adhesive capacity, persistence and beneficial effects. We initiated a structural investigation programme to visualize the LGG pili to understand its mechanism of attachment, architecture and how it differs from that of pathogenic bacteria. The LGG pili are made up of three different building blocks. Initially, we discovered the structure of a building block (SpaA) that forms the backbone of LGG pili and provided new insights about how the LGG assembles elongated spring-like pilus fibre (https://doi.org/10.1038/srep28664). The flexible yet stable pilus fibre help LGG to withstand environmental shear forces during the colonization in the gut. Subsequently, we discovered the structure of the largest building block (SpaC), which is mainly responsible for mediating attachment with the gut. The SpaC located at the pilus tip has a unique binding region with a new arm which is different from that of pathogens. The binding region in the SpaC can attach multiple extracellular matrix (ECM) molecules like collagen and mucin. The study explained how LGG has enhanced adhesive capacity and ability to inhibit pathogens attachment by the process known as competitive colonization (https://doi.org/10.1016/j.jsb.2020.107571). While this potent molecule (SpaC) and its property can be further exploited for the applications in improving health and controlling infections (e.g. anti-adhesion therapy), We have now discovered the structure of the smallest block (SpaB). The structural analysis of SpaB reveals mechanistic insights about its incorporation into the pili (https://doi.org/10.1016/j.crstbi.2020.11.001). With the high-resolution structure of all the building blocks, a complete architecture of pili has now become available for the first time from a probiotic. The structural knowledge from work may open up new avenues in probiotic engineering, vaccine delivery, and utilizing probiotic for promoting health benefits and combating infections.

For details,

 Crystal structure of the atypically adhesive SpaB basal pilus subunit: Mechanistic insights about its incorporation in lactobacillar SpaCBA pili (link https://www.sciencedirect.com/science/article/pii/S2665928X20300234?via%3Dihub)