Moyen amphi (LPS


07 Avr 2023


11h00 - 12h00

Albertus Viljoen (UC Louvain, Belgique)

Adhesion to host cells and tissues is an important first step in infection employed by many bacterial pathogens. In mycobacteria, surface hydrophobic properties and specialized receptor-ligand bonds determine how these pathogens adhere to host immune cells. We recently used fast quantitative imaging (QI) atomic force microscopy (AFM) combined with hydrophobic tips to quantitatively map hydrophobic properties of mycobacterial pathogens, at high spatial resolution1. We discovered that abundant polar outer membrane lipids modulate the nanoscale distribution of hydrophobicity on the bacterial surface, which could be modulated by treatments with specific antibiotics. This led us to hypothesize that the presence of nanodomains enriched in specific surface molecules have a functional role in pathogen-host interactions. We have now found support for this hypothesis by studying recognition of pathogenic mycobacteria by the pathogen recognition receptor DC-SIGN 2. By probing live mycobacteria with AFM tips modified with single tetramers of the soluble extracellular domain of DC-SIGN we observed that the receptor forms complexes with ligands on pathogenic and nonpathogenic mycobacteria. Moreover, the complexes are mechanically weak, rupturing at ~30 pN under physiological force loading rates. However, by relying on the specific force-extension signatures generated we could map the locations of single DC-SIGN ligands at a resolution of ~20 nm, which revealed concentration of ligands into dense nanodomains on pathogenic mycobacteria exclusively. Upon bacteria-host cell contact, ligand nanodomains induce the recruitment and clustering of DC-SIGN, resulting in mechanically stable adhesion. This work highlights the key role of clustering of both ligands on pathogenic bacteria and DC-SIGN host receptors in pathogen recognition, a mechanism that might be widespread in host-pathogen interactions.

1.           Viljoen, A., Viela, F., Kremer, L. & Dufrêne, Y. F. Fast chemical force microscopy demonstrates that glycopeptidolipids define nanodomains of varying hydrophobicity on mycobacteria. Nanoscale Horiz. 5, 944–953 (2020).

2.           Viljoen, A. et al. Nanoscale clustering of mycobacterial ligands and DC-SIGN host receptors are key determinants for pathogen recognition. Sci. Adv. accepted, (2023).