Marion Mathelié-Guinlet
Institut de Chimie et Biologie des Membranes et des Nano-Objets, CNRS UMR 5248, Université de Bordeaux, IPB, 33600 Pessac, France

“Atomic force microscopy: a window towards the molecular mechanisms driving bacterial colonization and resistance”

Living cells constantly interact with their environment via their surface that exhibits sophisticated functions notably mediated by proteins. The spatial organization and functional roles of proteins within the cell or interacting with their surroundings are crucial, yet largely unsolved, questions in cell biology. In the past decades, atomic force microscopy (AFM) has evolved into a multifunctional toolbox enabling the imaging and manipulation of cell surfaces and components with molecular resolution1. Combining AFM with advanced genetic manipulation, we have greatly contributed to the elucidation of the nanomechanical properties of proteins in the context of microbial adhesion and mechanosensing. During this talk, I will first focus on the key role of proteins in the overall mechanical behaviour of the bacterial envelope, which is the first target of various antibiotics. In the prototypical pathogen Escherichia coli, I notably unraveled the dual role of the Braun’s lipoprotein Lpp in defining cell envelope stiffness and drug sensitivity, i.e. by covalently connecting the outer membrane to the peptidoglycan and by precisely controlling the periplasmic space2. We will then address the key role of proteins in the force-driven microbial adhesion involved in biofilm-associated infections. Recently, I provided the first quantitative demonstration of a catch-bond (i.e. a counterintuitive strengthening with load) in living Gram-positive pathogens using AFM force-clamp spectroscopy3. Such shear-stress dependent behavior provides the pathogen with a mechanism to tightly control its adhesive function during colonization and infection. Finally, I will briefly discuss other strategies bacteria have evolved to escape immune system and persist within their targets, and some major technical improvement allowing our better understanding of microbial lifecycle.

1. Müller, D. J. & Dufrêne, Y. F. Nat. Nanotechnol. 3, 261–269 (2008).
2. Mathelié-Guinlet, M., Asmar, A. T., Collet, J.-F. & Dufrêne, Y. F. Nat. Commun. 11, 1789 (2020).
3. Mathelié-Guinlet, M. et al. Nat. Commun. 11, 5431 (2020).