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.
Antimicrobial resistance is a global threat that kills at least 75,000 people every year worldwide and causes extended hospital stays. In coming 10 years, it is projected to have huge health and economic burden on countries and the scarcity of available antibiotics further worsens the situation. It is a result of many confounding factors that ranges from indiscriminate antibiotic usage in humans, animals and agriculture and the rapid rate of emergence and dissemination of the resistant pathogens. This menace is challenging and urgent attention at many fronts such as antibiotic stewardship, strict regulations over antibiotics usage, large-scale surveillance and responsible public behavior. This demands international cooperation and integrated efforts under 'One-health' approach to effectively mitigate the issue of antimicrobial resistance.Here, we review the multifaceted nature of antimicrobial resistance and usefulness of the 'One-Health' approach to curb the origin and spread of antimicrobial resistance. The role of antibiotics and antimicrobial resistance has been discussed with examples citing the historical mistake of using antibiotics common between animal and humans. This generated resistance against last-resort antibiotics and multiplier effects against related classes of antibiotics. We highlight the effectiveness of hygiene in livestock rearing, careful antibiotic usage and large-scale surveillance of animals, humans and environment domains for understanding the emergence and spread of antimicrobial resistance.Further, we focus on the steps taken for mitigation of antimicrobial resistance that includes public awareness led successful ban of triclosan and the significant decrease in resistant pathogens due to strict antibiotic stewardship. We emphasize the positive role of inter-continental partnership such as Global Antibiotic Resistance Partnership and international collaboration for high-throughput surveillance and continuous data exchange for effective regulation of antimicrobial resistance. The last section underscores the need for bringing all the mitigation steps proposed in the earlier sections under an integrated approach called as One-health. 'One-Health' is a holistic and integrative approach that can help in effective participation of stakeholders from public, health care professionals and government to mitigate antimicrobial resistance. This is essential for effective control and structured framework to tackle the issue of antimicrobial resistance.
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