Speaker
Description
Bacterial infections pose a serious challenge due to antibiotic resistance; bacteria rapidly adapt to drugs used in clinical practice, resulting in high mortality rates. A deep understanding of the molecular mechanisms by which bacterial pathogens enter host cells provides a foundation for developing new, non-antibiotic strategies to combat these pathogens.
Cell surface is covered with complex carbohydrates (composed of several monosaccharides, i.e. glycans) that form an informational layer facilitating intercellular communication; in the course of acquiring pathogenicity, bacteria have evolved to recognize this host "glycocode". Experimental evidence indicates that lectins, carbohydrate-binding proteins, play a crucial role in the virulence factor arsenal of pathogenic bacteria, for example P. aeruginosa. They selectively bind to carbohydrate moieties of glycolipids and glycoproteins on the host cell surface. This binding induces complex changes in the state of membrane receptors within the membrane plane and triggers a cellular response that leads to the uptake or internalization of the resulting complex. Biochemical and biophysical methods are employed to elucidate the molecular mechanisms underlying the recognition of the host by pathogen virulence factors.
To decipher molecular aspects of the host recognition by virulence factors of a pathogen and bacterial uptake, e.g. identifying the membrane receptors targeted by a lectin and determining how lectin binding affects the composition of membrane domains, biochemical and biophysical methods, for instance fluorescent microscopy, mass spectrometry and immunoprecipitation, are employed. However, obtaining a detailed atomic-level information required for a profound understanding of complex formation within the context of the plasma membrane remains highly challenging. These difficulties stem primarily from the nature of glycans, which are characterized by structural heterogeneity and high intrinsic conformational flexibility.
Molecular dynamics methods offer a unique tool for tracking time-dependent changes in the conformational ensembles of aglycone-linked complex glycans, as well as their interactions with other plasma membrane components and bacterial lectins [1]. Furthermore, computational modeling enables the relatively rapid variation of conditions, allowing for the simulation of plasma membrane remodeling or alterations in glycosylation profiles.
In the current communication, we present examples illustrating the structural aspects of the interactions between P. aeruginosa lectins (LecA and LecB) with their glycolipids and glycoproteins receptors, thereby demonstrating the role of carbohydrate presentation on the plasma membrane surface in the processes of pathogen-host recognition [2,3].
References:
1. Perez S. & Makshakova O. Multifaceted Computational Modeling in Glycoscience. Chem. Rev. 2022, 122(20), P. 15914-15970. doi: 10.1021/acs.chemrev.2c00060.
2. Kociurzynski R., Makshakova O., Knecht V., Römer W. Multiscale Molecular Dynamics Studies Reveal Different Modes of Receptor Clustering by Gb3-Binding Lectins. J Chem Theory Comput. 2021, 17(4), P.2488-2501. doi: 10.1021/acs.jctc.0c01145.
3. Kittel A., Makshakova O., Hauerwas M., Edel N., Knickmeier N., Tomisch J., Aljohmani A., Yildiz D., Peyronnet R., Römer W. LecB from Pseudomonas Aeruginosa Modulates Piezo1 Currents and Localization in a Time-Dependent Manner. Cell Mol Life Sci. 2025, 82(1), P.399. doi: 10.1007/s00018-025-05934-z.