Quantifying and Engineering Mucus Adhesion of Probiotics

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.