The trillions of microbes hosted by humans can dictate health or illness depending on a multitude of genetic, environmental, and lifestyle factors that help define the human ecosystem. As the human microbiota is characterized, so can the interconnectivity of microbe-host-disease be realized and manipulated. Designing microbes as therapeutic agents can not only enable targeted drug delivery but also restore homeostasis within a perturbed microbial community. Used for centuries in fermentation and preservation of food, lactic acid bacteria (LAB) have a long history of safe, and occasionally health promoting, interactions with the human gut, making them ideal candidates for engineered functionality. This review outlines available genetic tools, recent developments in biomedical applications, as well as potential future applications of synthetic biology to program LAB-based therapeutic systems.
Figure S1. Growth of E. coli after gene deletions intended to lower basal growth on MM phe,init . (a.-d.) Select aminotransferases with reported promiscuous activity on phenylalanine were deleted in an attempt to reduce the level of basal growth seen by wild-type E. coli on MM phe,init . Each deletion strain showed no changes in
Mucus in the gastrointestinal (GI) tract is the primary point-of-interaction between humans and their gut microbiota. This not only intimates that mucus ensures protection against endogenous and exogenous opportunists but provision 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 dosedependent adhesion metrics. Surface proteins and cell components known to influence mucoadhesion were then heterologously expressed or altered in Lactococcus lactis MG1363 and E. coli Nissle 1917 to control mucus-binding capacity, avidity, and cooperativity.
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