한빛사논문
- 조회249
Elvin Koh 1,2,3,7, In Young Hwang1,2,3,7, Hui Ling Lee1,2,3, Ryan De Sotto1,2,3, Jonathan Wei Jie Lee 1,2,4, Yung Seng Lee 1,2,5, John C. March6 & Matthew Wook Chang 1,2,3,*
1NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore. 2 Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 3Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 4Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 5Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 6Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA. 7These authors contributed equally: Elvin Koh, In Young Hwang.
*Corresponding author.
Abstract
Clostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. The pathogenesis of CDI is intrinsically related to the ability of C. difficile to shuffle between active vegetative cells and dormant endospores through the processes of germination and sporulation. Here, we hypothesise that dysregulation of microbiome-mediated bile salt metabolism contributes to CDI and that its alleviation can limit the pathogenesis of CDI. We engineer a genetic circuit harbouring a genetically encoded sensor, amplifier and actuator in probiotics to restore intestinal bile salt metabolism in response to antibiotic-induced microbiome dysbiosis. We demonstrate that the engineered probiotics limited the germination of endospores and the growth of vegetative cells of C. difficile in vitro and further significantly reduced CDI in model mice, as evidenced by a 100% survival rate and improved clinical outcomes. Our work presents an antimicrobial strategy that harnesses the host-pathogen microenvironment as the intervention target to limit the pathogenesis of infection.
논문정보
- Research article
- 2022년 07월 (BRIC 등록일 2022-10-28)
- 국외 연구진
- 생명과학 > 생물공학
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