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Colloquium Natural & Life Sciences - Winfried Römer & Yavuz Öztürk

Prof. Dr. Winfried Römer

Biology
Freiburg University, BIOSS, FRIAS

Dr. Yavuz Öztürk

Biochemistry
Freiburg University

Bacterial Pathogenicity
When Jun 21, 2022
from 11:30 AM to 12:30 PM
Where Pathology Lecture Hall
Contact Name
Attendees Universitätsoffen / open to university members
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Session Topic: Bacterial Pathogenicity


Topic Winfried Römer -The impact of bacterial lectins on host cell physiology

 The bacterium P. aeruginosa emerged as a major human opportunistic pathogen during the past decades, maybe as a consequence of its resistance to antibiotics and disinfectants.
It is able to cause severe infections of the respiratory and urinary tract, skin and eye, predominantly in immune compromised patients. P. aeruginosa has a vast range of virulence factors, amongst them, the two bacterial lectins LecA and LecB, which, by virtue of their sugar binding, contribute to the pathogens’ host specificity and adherence to host cells. Whereas LecA is galactophilic, LecB displays a very high affinity to L-fucose.

We have demonstrated that the interactions of LecA with the host cell glycosphingolipid Gb3 were sufficient to induce the engulfment of the bacterium, independent of actin polymerization. The absence of one of these two factors led to a reduction of invasiveness of the bacterium by around 70 %. In collaboration with research groups from Switzerland and France, we have identified a sugar complex from galactoside-conjugated arrays that prevents LecA from docking onto its host cell receptor by binding to the bacterial protein with great precision. In tests conducted in cell culture, we could reduce the cellular invasion of human lung epithelial cells by P. aeruginosa by more than 80 % when using the inhibitor in nano-molar concentrations.

A better understanding of the mode of action of natural lectins may encourage their future use as tools in therapeutic approaches. Currently, tailor-made lectins and lectin chimeras with controlled valency and specificity are designed based on natural examples and will be further investigated in basic research as well as in applications.

Topic Yavuz Öztürk - How bacteria sense extracellular metabolites

Metabolic sensing is a crucial prerequisite for adjusting cell physiology to rapidly changing environments. In bacteria, the response to intra- and extracellular ligands is primarily controlled by transcriptional regulators, which activate or repress gene expression and thus ensure metabolic adaptation. However, translational control also contributes to cellular adaptation and the importance of ribosomal arrest peptides in mediating the response to intracellular ligands has been shown in a few cases. In the current study, we demonstrate that the arrest-peptide containing protein CutF regulates the response to extracellularly accumulating Cu, a potentially toxic trace element. Our data show that CutF acts as a Cu sensor that is co-translationally secreted. In the presence of Cu, the C-terminal arrest peptide of CutF causes ribosomal stalling, which allows the expression of downstream cutO gene, encoding for a Cu-detoxifying multi-copper oxidase. Bioinformatic analyses reveal that CutF-like proteins are widely distributed in bacteria and often located upstream of genes involved in Cu homeostasis. In summary, our data reveal a largely conserved translational control mechanism that allows to integrate the concentration of extracellular nutrients into metabolic adaptation.