Structural basis of probiotic LGG adhesion to the gut

Use of antibiotics is not only developing resistance but also destroying the gut microbiota that we earned since birth. Hence the search for alternative approaches including the use of probiotics is being explored. The probiotics are well known for their beneficial effects, including inhibition of colonization by harmful microbes. One of the vital criteria in choosing probiotics is they must have the ability to attach to the gut lines. We used probiotic Lactobacillus rhamnosus GG (LGG), which 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 in LGG is a major contributing factor for its adhesive capacity and persistence in the gut. We used X-ray crystallography and imaging techniques to visualize the LGG pili to understand its mechanism of attachment and how it differs from that of pathogenic bacteria. We previously discovered the structure of a building block (https://www.nature.com/articles/srep28664 ) that forms the backbone of LGG pili, and provided new insights about how the LGG assembles elongated spring-like pilus fibre by molecular welding (isopeptide bonds) between and within the blocks. The flexible yet stable pilus fibre helps LGG to withstand environmental shear forces during the colonization in the gut. We have now discovered the structure of another large building block (SpaC) which is mainly responsible for mediating attachment with the gut lines. 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 explains how LGG has enhanced adhesive capacity and able to inhibit pathogens attachment by the process known as competitive colonization. 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).

For details: Crystal structure of lactobacillar SpaC reveals an atypical five-domain pilus tip adhesin: Exposing its substrate-binding and assembly in SpaCBA pili