Protein folding modulates the adhesion strategy of Gram positive pathogens

• DOI: 10.1101/743393
• Publication Date: 2019-08-22T09:54:01Z
• Authors: Alvaro Alonso-Cab...; Daniel J. Echelman; Rafael Tapia-Rojo; Shubhasis Haldar; Edward C. Eckels; Julio M. Fernandez
• Keywords: Thioester

Gram positive bacteria colonize mucosal tissues against large mechanical perturbations, such as coughing, which generate shear forces that exceed the ability of non-covalent bonds to remain attached. To overcome these challenges, pathogen Streptococcus pyogenes utilizes protein Cpa, a pilus tip-end adhesin equipped with Cys-Gln thioester bond. The reactivity this bond towards host surface ligands enables covalent anchoring bacterium, allowing it resist shocks; however, colonization also requires cell migration and spreading over surfaces. molecular mechanisms underlying seemingly incompatible requirements unknown. Here, we demonstrate magnetic tweezers force spectroscopy assay resolves dynamics Cpa under force. While folded at < 6 pN, reacts reversibly amine ligands, common occurrence in inflammation sites; unfolding exposure higher than 35 pN blocks entirely. We propose folding-coupled switch allows hop sample low (nomadic mobility phase), yet gets covalently anchored place while stress (locked phase). dub “smart bonds”, adding novel class known repertoire adhesion strategies include slip bonds, catch bonds.