Synthetic bacterial therapies for intestinal diseases based on quorum-sensing circuits

Zhuoce Dang; Mengxue Gao; Lina Wang; Jiahao Wu; Yufei Guo; Zhixin Zhu; He Huang; Guangbo Kang

doi:10.1016/j.biotechadv.2023.108142

Synthetic bacterial therapies for intestinal diseases based on quorum-sensing circuits

Biotechnol Adv. 2023 Jul-Aug:65:108142. doi: 10.1016/j.biotechadv.2023.108142. Epub 2023 Mar 26.

Authors

Zhuoce Dang¹, Mengxue Gao¹, Lina Wang¹, Jiahao Wu¹, Yufei Guo¹, Zhixin Zhu¹, He Huang², Guangbo Kang³

Affiliations

¹ Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China.
² Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China. Electronic address: huang@tju.edu.cn.
³ Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China; Institute of Shaoxing, Tianjin University, Zhejiang 312300, China. Electronic address: guangbo_kang@tju.edu.cn.

PMID: 36977440
DOI: 10.1016/j.biotechadv.2023.108142

Abstract

Bacterial therapy has become a key strategy against intestinal infectious diseases in recent years. Moreover, regulating the gut microbiota through traditional fecal microbiota transplantation and supplementation of probiotics faces controllability, efficacy, and safety challenges. The infiltration and emergence of synthetic biology and microbiome provide an operational and safe treatment platform for live bacterial biotherapies. Synthetic bacterial therapy can artificially manipulate bacteria to produce and deliver therapeutic drug molecules. This method has the advantages of solid controllability, low toxicity, strong therapeutic effects, and easy operation. As an essential tool for dynamic regulation in synthetic biology, quorum sensing (QS) has been widely used for designing complex genetic circuits to control the behavior of bacterial populations and achieve predefined goals. Therefore, QS-based synthetic bacterial therapy might become a new direction for the treatment of diseases. The pre-programmed QS genetic circuit can achieve a controllable production of therapeutic drugs on particular ecological niches by sensing specific signals released from the digestive system in pathological conditions, thereby realizing the integration of diagnosis and treatment. Based on this as well as the modular idea of synthetic biology, QS-based synthetic bacterial therapies are divided into an environmental signal sensing module (senses gut disease physiological signals), a therapeutic molecule producing module (plays a therapeutic role against diseases), and a population behavior regulating module (QS system). This review article summarized the structure and function of these three modules and discussed the rational design of QS gene circuits as a novel intervention strategy for intestinal diseases. Moreover, the application prospects of QS-based synthetic bacterial therapy were summarized. Finally, the challenges faced by these methods were analyzed to make the targeted recommendations for developing a successful therapeutic strategy for intestinal diseases.

Keywords: Gene module; Intestinal diseases; Quorum sensing; Synthetic bacterial therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Bacteria
Gastrointestinal Microbiome* / genetics
Gene Regulatory Networks
Humans
Intestinal Diseases*
Quorum Sensing / genetics