Architecture of cell–cell junctions in situ reveals a mechanism for bacterial biofilm inhibition
Charlotte E. Melia, Jani Reddy Bolla, Stefan Katharios-Lanwermeyer, Daniel B. Mihaylov, Patrick C. Hoffmann, Jiandong Huo, Michael R. Wozny, Louis M. Elfari, Jan Böhning, Ashleigh N. Morgan, Charlie J. Hitchman, Raymond J. Owens, Carol V. Robinson, George A. O’Toole, Tanmay A. M. Bharat
Abstract
biofilms at intact cell-cell junctions. Combining our in situ observations at cell-cell junctions with biochemistry, native mass spectrometry, and cellular imaging, we demonstrate that CdrA forms an extended structure that projects from the outer membrane to tether cells together via polysaccharide binding partners. We go on to show the functional importance of CdrA using custom single-domain antibody (nanobody) binders. Nanobodies targeting the tip of functional cell-surface CdrA molecules could be used to inhibit bacterial biofilm formation or disrupt preexisting biofilms in conjunction with bactericidal antibiotics. These results reveal a functional mechanism for cell-cell interactions within bacterial biofilms and highlight the promise of using inhibitors targeting biofilm cell-cell junctions to prevent or treat problematic, chronic bacterial infections.