DNA-programmed responsive microorganism assembly with controlled patterns and behaviors

Abstract

Programming microorganism adhesions to engineer multicellular microbial communities holds promise for synthetic biology and medicine. Current chemical and genetic engineering approaches often lack specificity or require engineered bacteria, making the design of responsive interactions challenging. Here, we demonstrate the use of functional DNA as programmable surface receptors to regulate the patterns and behaviors of microbial communities. Using metabolic labeling and hydrophobic insertion, we modified various microorganisms with DNA, including Gram-positive and Gram-negative bacteria, and dormant spores. By incorporating distinct sequences, we achieved precise spatial control of bi- and tricomponent microbial assemblies, forming diverse morphologies like core-shell and selective clusters. Stimuli-responsive clustering was successfully realized using aptamers, strand displacement, and reverse-Hoogsteen base pairing, with oligonucleotides or small molecules as exogenous cues. This work extends the use of functional DNA to control microbial interactions, enabling living communities with dynamic biofunctions, such as biofilm formation, antibiotic sensitivity, and quorum sensing, in response to biological triggers.