Deciphering the role of lectins in surface adhesion and virulence of Pseudomonas aruginosa

Post-doc project

Bacteria can adhere to both abiotic and cellular surfaces. However, the cues that regulate the switch from an individual motile lifestyle to a sessile one are not clear, and the mechanisms of this transition are complex. On surfaces, bacteria form communities called biofilms, in which a self-produced extracellular matrix acts as a glue and shields bacteria from the environment. In industrial settings, biofouling is a costly issue, which leads to increased drag in pipes, clogging of membranes and unwanted contamination. In healthcare, biofilm formation plays a crucial role in the development of antibiotic resistance. The biofilm-former Pseudomonas aeruginosa is part of a family of microorganisms exhibiting multi-drug resistant virulence, responsible for most hospital-acquired infections. These so-called nosocomial infections account for the death of nearly 9000 persons/year in France only. P. aeruginosa is a versatile opportunistic pathogen, responsible for acute and chronic lung infections in immuno-compromised patients, but also involved in urinary tract, wound and systemic infections.

Bacterial lectins are sugar-binding proteins that mediate adhesion to host surfaces, and are also important for biofilm formation. In Pseudomonas aeruginosa, lectins LecA and LecB are known to be key pathogenicity factors, yet their exact role in surface colonization and their implication in virulence pathways are unclear.

Here we propose to use unique experimental approaches developed over the past few years at LIPhy, combined to the expertise of lectin specialists at CERMAV, in order to decipher the exact role of P. aeruginosa soluble lectins LecA and LecB in adhesion and virulence activation. LecA and LecB structures suggests that they function as tetramers, and could create cell-bacteria, matrix-bacteria, and bacteria-bacteria interactions, which could explain why they are important for adhesion as well as biofilm cohesion.

The goal of the proposed project is to use an integrative cross-disciplinary approach involving surface functionalization, microscopy, time-resolved force measurements and microbiology tools in order to unravel the role of P. aeruginosa lectins in early biofilm formation and pathogenicity, thus identifying new targets for antimicrobial strategies.