Author
Listed:
- Po-Yin Chen
(Academia Sinica
Academia Sinica and National Defense Medical Center)
- Yung-Chih Chen
(Academia Sinica)
- Po-Pang Chen
(Academia Sinica
National Yang Ming Chiao Tung University)
- Kuan-Ting Lin
(Academia Sinica
National Yang-Ming Chao-Tung University and Academia Sinica)
- Karen Sargsyan
(Academia Sinica)
- Chao-Ping Hsu
(Academia Sinica
National Center for Theoretical Sciences
National Taiwan University)
- Wei-Le Wang
(Academia Sinica
Academia Sinica and National Defense Medical Center
National Yang-Ming Chao-Tung University and Academia Sinica)
- Kuo-Chiang Hsia
(Academia Sinica
Academia Sinica and National Defense Medical Center
National Yang Ming Chiao Tung University)
- See-Yeun Ting
(Academia Sinica
Academia Sinica and National Defense Medical Center
National Taiwan University)
Abstract
Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library. Leveraging the potency of the bacterial type IV secretion system—a contact-dependent DNA delivery nanomachine—we have established a positive feedback mechanism to selectively enrich for bacteria displaying nanobodies that target antigen-expressing cells. Our platform successfully identified functional CAMs capable of recognizing three distinct outer membrane proteins (TraN, OmpA, OmpC), demonstrating its efficacy in CAM discovery. This approach holds promise for engineering bacterial cell-cell adhesion, such as directing the antibacterial activity of programmed inhibitor cells toward target bacteria in mixed populations.
Suggested Citation
Po-Yin Chen & Yung-Chih Chen & Po-Pang Chen & Kuan-Ting Lin & Karen Sargsyan & Chao-Ping Hsu & Wei-Le Wang & Kuo-Chiang Hsia & See-Yeun Ting, 2024.
"A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria,"
Nature Communications, Nature, vol. 15(1), pages 1-16, December.
Handle:
RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51017-1
DOI: 10.1038/s41467-024-51017-1
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