Quantifying and Engineering Mucus Adhesion of Probiotics.,ACS Synthetic Biology

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Quantifying and Engineering Mucus Adhesion of Probiotics.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-01-13 , DOI: 10.1021/acssynbio.9b00356
Zachary J S Mays ₁ , Todd C Chappell ₁ , Nikhil U Nair ₁

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Mucus in the gastrointestinal (GI) tract is the primary point-of-interaction between humans and their gut microbiota. This intimates that mucus not only ensures protection against endogenous and exogenous opportunists but also provisions for the human microbiota to reside and flourish. With the emergence of living therapeutics, engineered microbes can deliver and produce increasingly complex medicine, and controlling the mucoadhesive properties of different microbial chassis can dictate dose-response in a patient. Here we present a redesigned, in vitro, plate-based assay to measure the mucus adhesion of various probiotics. Cell-mucus interactions were isolated by immobilizing mucus to the plate surface. Binding parameters were derived for each probiotic strain by measuring cell adhesion over a wide range of cell concentrations, providing dose-dependent adhesion metrics. Surface proteins and cell components known to influence mucoadhesion were then heterologously expressed or altered in Lactococcus lactis MG1363 and Escherichia coli Nissle 1917 to control mucus-binding capacity, avidity, and cooperativity.

中文翻译：

定量和工程化益生菌的粘液黏附。

胃肠道（GI）中的粘液是人类与其肠道菌群之间的主要相互作用点。这表明粘液不仅可以确保免受内源性和外源性机会主义者的侵害，而且还可以为人类微生物群的生存和繁衍提供条件。随着活性疗法的出现，工程微生物可以提供和生产越来越复杂的药物，并且控制不同微生物底物的粘膜粘附特性可以决定患者的剂量反应。在这里，我们提出了一种重新设计的，基于板的体外测定法，以测量各种益生菌的粘液粘附力。通过将粘液固定在板表面上来分离细胞-粘液相互作用。通过测量各种细胞浓度下的细胞粘附力，得出每种益生菌菌株的结合参数，提供剂量依赖性的粘附指标。然后在乳酸乳球菌MG1363和大肠杆菌Nissle 1917中异源表达或改变已知影响粘膜粘附的表面蛋白和细胞组分，以控制粘液结合能力，亲合力和协同作用。

更新日期：2020-01-13

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