NIR light-responsive bacteria with live bio-glue coatings for precise colonization in the gut

Abstract

Recombinant bacterial colonization plays an indispensable role in disease prevention, alleviation, and treatment. Successful application mainly depends on whether bacteria can efficiently spatiotemporally colonize the host gut. However, a primary limitation of existing methods is the lack of precise spatiotemporal regulation, resulting in uncontrolled methods that are less effective. Herein, we design upconversion microgels (UCMs) to convert near-infrared light (NIR) into blue light to activate recombinant light-responsive bacteria (Lresb) in vivo, where autocrine ''functional cellular glues'' made of adhesive proteins assist Lresb inefficiently colonizing the gut. The programmable engineering platform is further developed for the controlled and effective colonization of Escherichia coli Nissle 1917 (EcN) in the gut. The colonizing bacteria effectively alleviate DSS-induced colitis in mice. We anticipate that this approach could facilitate the clinical application of engineered microbial therapeutics to accurately and effectively regulate host health.

Programming the lifestyles of engineered bacteria for cancer therapy

“…Besides, optogenetics provides a promising approach for gene-and cell-based therapies via precisely manipulating various cellular activities with high spatiotemporal resolution [63]. And the deep tissue penetration of NIR light offers a non-invasive treatment modality for a variety of diseases [64,65]. The illumination intensity and pattern of multiple light spots, especially lasers, can be easily controlled by computer algorithms, enabling neuroscientists to stimulate hundreds of precisely targeted neurons simultaneously [66].…”

Native and Engineered Probiotics: Promising Agents against Related Systemic and Intestinal Diseases

“…Functions/Benefits Reference express autotransporter 43 adhesins antigen use optogenetics to activate secretion against colitis/precise spatiotemporal colonization [198] express IL-10 phone visual diagnosis and optogenetics based secretion against colitis/mobile health service [199] express GLP-1 analog GLP-1 analog diminishes food intake against obesity [200] express N-acylphosphatidylethanolamines N-acylphosphatidylethanolamines induce satiety against obesity [201] express antimicrobial peptides antimicrobial peptides target and kill Enterococcus against vancomycin-resistant Enterococcus [202] develop a synthetic genetic system sense and kill Pseudomonas aeruginosa against Pseudomonas aeruginosa [203] express N-acylphosphatidylethanolamines reduce body weight, liver inflammation, fibrosis and atherosclerotic necrosis against cardiovascular metabolic disease [204] express PQQ and other metabolizing enzymes relieve oxidative stress against heavy metal toxicity/iron deficiency/fructoseinduced dyslipidemia/hyperglycemia/hepatic steatosis [205][206][207] express l-arg biosynthetic enzyme exhausts ammonia for L-arginine biosynthesis against hyperammonemia [208] express phenylalanine ammonia lyase and L-amino acid deaminase consume phenylalanine within the gastrointestinal tract against PKU [209] Express adjuvant therapeutic factors express 5-ALA 5-ALA contributes to photodynamic therapy against cancer [210] express CAT increase the production of O2 contributing to radiotherapy against cancer [211] produce…”

“…This process involved screening for acetyl-CoA acetyltransferase, 3HB-CoA dehydrogenase, and thioesterase isozymes, inserting the optimum 3HB synthesis system into the EcN genome, and knocking out adhE or ldhA to inhibit the branch pathways and increase 3HB production, thereby alleviating colitis. Optogenetics has also been combined with probiotics, using upconversion microgels to convert near-infrared light into local visible blue light [ 198 ]. Through this technology, the recombinant EcN is activated to secrete autotransporter 43 adhesins antigen, achieving precise spatiotemporal regulation, which effectively alleviates colitis in mice [ 198 ].…”

“…Optogenetics has also been combined with probiotics, using upconversion microgels to convert near-infrared light into local visible blue light [ 198 ]. Through this technology, the recombinant EcN is activated to secrete autotransporter 43 adhesins antigen, achieving precise spatiotemporal regulation, which effectively alleviates colitis in mice [ 198 ]. Recently, recombinant IL-10-secreting EcN has been used in the optotheranostic nanosystem for UC as a real-time intervention module for long-lasting relief of the intestinal inflammatory responses [ 199 ], making it possible to diagnose and treat intestinal inflammation at home.…”

Augmenting the Signal Peptide of the Ag43 Autotransporter for the improved heterologous display of sfGFP using Fluorescence-Activated Cell Sorting (FACs)-assisted natural selection

“…To enable the programming of cells to fabricate engineered living materials (ELMs) (Duraj-Thatte et al, 2021; Glass and Riedel-Kruse, 2018; Jin and Riedel-Kruse, 2018; Widmaier et al, 2009), deliver protein therapeutics, (Cui et al, 2021; Ho et al, 2018; Veiga et al, 2003; Wu et al, 2013) test mutant protein variants faster (Alessa et al, 2019; Daugherty et al, 2000; Ling et al, 2022, 2018; Starr et al, 2020; Su et al, 2021, 2018; Warszawski et al, 2019), optimize bioprocess parameters (Heng et al, 2022; Ling et al, 2020), perform biochemical reactions(Lindroos et al, 2019; Muñoz-Gutiérrez et al, 2014) and construct biosensors (Kylilis et al, 2019; VanArsdale et al, 2020), require the production, display or secretion of proteins in both eukaryotes and prokaryotes. Escherichia coli ( E. coli ) remains one of the best-characterized model organisms for engineering to secrete proteins into the extracellular environment (Kleiner-Grote et al, 2018).…”