High force catch bond mechanism of bacterial adhesion in the human gut

• DOI: 10.1038/s41467-020-18063-x
• Publication Date: 2020-08-28T10:09:48Z
• Authors: Zhaowei Liu; Haipei Liu; Andrés M. Vera; Rafael C. Bernardi; Philip Tinnefeld; Michael A. Nash
• Keywords: Force Spectroscopy

Abstract Bacterial colonization of the human intestine requires firm adhesion bacteria to insoluble substrates under hydrodynamic flow. Here we report molecular mechanism behind an ultrastable protein complex responsible for resisting shear forces and adhering cellulose fibers in gut. Using single-molecule force spectroscopy (SMFS), FRET (smFRET), dynamics (MD) simulations, resolve two binding modes three unbinding reaction pathways a mechanically R. champanellensis ( Rc ) Dockerin:Cohesin (Doc:Coh) complex. The assembles discrete with significantly different mechanical properties, one breaking at ~500 pN other ~200 loading rates from 1-100 nN s −1 . A neighboring X-module domain allosterically regulates interaction inhibits low-force high rates, giving rise catch bonding that manifests ramp protocols. Multi-state Monte Carlo simulations show strong agreement experimental results, validating proposed kinetic scheme. These results explain mechanistically how gut microbes regulate cell strength stress through intricate mechanisms including dual-binding modes, allostery bonds.