Multi-functional role of an important Mucus binding protein in host-microbe interactions and non-antibiotic protection from pathogens

Kumar Siddharth Singh, Sudarshan Kumar, Ashok Kumar Mohanty, Sunita Grover, Jai Kumar Kaushik

Overview

Probiotic surface adhesins such as Mucus binding proteins are important modulators in host-microbe interactions, which remains unexplored. Here, we dissect the mechanism of this protein's action and also its efficacy as a potential nutraceutical, when used as controlled release microspheres.

Summary

We provide insights into the protein mode of action and its efficacy in competitive exclusion of pathogens. This is important because the mechanism is largely unknown and the controlled release formulations of this protein show high delivery and persistence in gut conditions, thereby proving their significance as a potential nutraceutical in prevention from gastrointestinal pathogens.

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Author Comments

Kumar Siddharth Singh
Kumar Siddharth Singh
Helmholtz Centre for Infection Research
Scientist
Braunschweig, Braunschweig | Germany
It was very interesting to work around our central theme that 'non-antibiotic interventions' are urgently needed to prevent gastrointestinal infections. I could get a lot of insights into this protein and its significance in infection prevention, even when used in truncated form. An absolutely satisfying and enriching experience ! Kumar Siddharth Singh

Mechanistic insights into the host-microbe interaction and pathogen exclusion mediated by the Mucus-binding protein of Lactobacillus plantarum.

Authors:
Kumar Siddharth Singh
Kumar Siddharth Singh
Helmholtz Centre for Infection Research
Scientist
Braunschweig, Braunschweig | Germany

Sci Rep 2018 09 21;8(1):14198. Epub 2018 Sep 21.

Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal, 132001, Haryana, India.

Surface adhesins of pathogens and probiotics strains are implicated in mediating the binding of microbes to host. Mucus-binding protein (Mub) is unique to gut inhabiting lactic acid bacteria; however, the precise role of Mub proteins or its structural domains in host-microbial interaction is not well understood. Last two domains (Mubs5s6) of the six mucus-binding domains arranged in tandem at the C-terminus of the Lp_1643 protein of Lactobacillus plantarum was expressed in E. coli. Mubs5s6 showed binding with the rat intestinal mucus, pig gastric mucins and human intestinal tissues. Preincubation of Mubs5s6 with the Caco-2 and HT-29 cell lines inhibited the binding of pathogenic enterotoxigenic E. coli cells to the enterocytes by 68% and 81%, respectively. Pull-down assay suggested Mubs5s6 binding to the host mucosa components like cytokeratins, Hsp90 and Laminin. Mubs5s6 was predicted to possess calcium and glucose binding sites. Binding of Mubs5s6 with these ligands was also experimentally observed. These ligands are known to be associated with pathogenesis suggesting Mub might negotiate pathogens in multiple ways. To study the feasibility of Mubs5s6 delivery in the gut, it was encapsulated in chitosan-sodium tripolyphosphate microspheres with an efficiency of 65% and release up to 85% in near neutral pH zone over a period of 20?hours. Our results show that Mub plays an important role in the host-microbial cross-talk and possesses the potential for pathogen exclusion to a greater extent than mediated by L. plantarum cells. The functional and technological characteristics of Mubs5s6 make it suitable for breaking the host-pathogen interaction.

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Source
http://dx.doi.org/10.1038/s41598-018-32417-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155027PMC
September 2018
17 Reads
2 Citations
5.078 Impact Factor

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