Kong Yuhan, Du Qi, Zhao Dan, Wen Yujian, Zhang Tianqing, Geng Zhiwang, Ying Maben, Wei Bryan, Si Tong, Tian Ye, Li Feng, Nie Zhou, Xing Hang
Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo and Biosensing, Hunan Provincial Key Laboratory of Bio-macromolecular Chemical Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
Yiyang Medical College, Yiyang 413002, China.
Sci Adv. 2025 Jun 13;11(24):eads8651. doi: 10.1126/sciadv.ads8651.
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.
对微生物黏附进行编程以构建多细胞微生物群落,这对合成生物学和医学而言颇具前景。当前的化学和基因工程方法往往缺乏特异性,或者需要经过工程改造的细菌,这使得设计响应性相互作用颇具挑战性。在此,我们展示了使用功能性DNA作为可编程表面受体来调节微生物群落的模式和行为。通过代谢标记和疏水插入,我们用DNA修饰了各种微生物,包括革兰氏阳性菌和革兰氏阴性菌以及休眠孢子。通过纳入不同序列,我们实现了对二元和三元微生物组装体的精确空间控制,形成了如核壳和选择性簇等多种形态。利用适体、链置换和反向Hoogsteen碱基配对,成功实现了刺激响应性聚集,以寡核苷酸或小分子作为外源信号。这项工作扩展了功能性DNA在控制微生物相互作用方面的应用,使活的群落能够响应生物触发因素而具有动态生物功能,如生物膜形成、抗生素敏感性和群体感应。
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