Nanomechanics of the molecular complexes between the staphylococcal adhesins Aap and SdrC/SdrD, and corneocytes

Details

Supervisors

Dufrêne Yves ; Chantraine Constance

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries, à finalité spécialisée

Abstract

Modern health care systems have to deal with an expanding number of nosocomial infections and the increase of antimicrobial resistance, especially linked to Staphylococcus aureus and Staphylococcus epidermidis based biofilms. Therefore the understanding of the interaction mechanisms occurring between bacterial cells and their host during infection process is a major challenge in microbiology and in health care. The first step for infection and colonization is cell adhesion, notably mediated by structurally and functionally diverse molecules, known as adhesins which are present on the bacterial cell wall. The aim of this master thesis is to gain novel insights into the nanoscale interaction forces between the two pathogens S. aureus and S. epidermidis, and the human skin. In particular, we sought to better understand the role of bacterial adhesins and skin ligands in the bacterial-skin adhesion, taking advantage of Atomic Force Microscopy (AFM). The interactions between S. aureus and S. epidermidis cells with healthy human corneocytes shows different types of adhesion patterns. For S. epidermidis cells, the interaction resulted in strong adhesion forces (~1 nN) and often multiple interactions (~2 nN, ~3 nN). The adhesion to corneocytes was mediated by to the Accumulation associated protein (Aap) whose B domain repeats unfold upon pulling resulting in a typical sawtooth pattern. Control experiments using a S. epidermidis mutant strain lacking Aap protein, showed no adhesion, thus confirming the involvement of specific adhesin-ligand complexes in the adhesion process. For S. aureus, two adhesins which belong to the serine-aspartate repeat family were investigated: SdrC and SdrD. These adhesins adhere both to corneocytes but with different behaviors. SrdC bind with strong adhesion forces (~2 nN) and simple interactions, while SdrD also bind with strong adhesion forces (> 2nN) and multiple interactions breaking in series or in parallel were observed. The understanding of these adhesion mechanisms could pave the way for the design of dedicated inhibitors.