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Karina Persson Lab

Research group Our group studies structure and function of proteins involved in bacterial virulence.

We are surrounded by bacteria. The vast majority of them live in symbiosis with us but there are a few, the pathogens, which pose danger to our health. This applies to both bacteria that come from the outside, for example via food or water, and those that live in our intestine, in our mouth on or our skin. The problem with bacterial pathogens is that they have become increasingly resistant to antibiotics, and in some cases there are no remaining options for treatment.

Due to the increase in antibiotic resistance, a completely new palette of antibacterial substances is required. With this background, it is important to investigate more bacterial virulence factors and molecular pathways that can serve as alternative targets.

Bacteria are divided into different phyla. Those that belong to the phylum proteobacteria are the best studied as the most common laboratory model, Escherichia coli, belongs to this phylum. Still, there are reaction pathways that are not fully understood. In our intestines we have kilograms of bacteria, and many of them represent the phylum bacteroidetes. Because bacteria of this phylum historically have been more difficult to grow in laboratory environments, they are not so well studied-many of their virulence factors and biochemical pathways are unknown.

E. coli and its close relatives express protein polymers, type-I fimbriae, on their surfaces. These are well characterized both structurally and functionally and are promising targets for the design of new antibiotics. Bacteria from the bacteroidetes phylum instead express type-V fimbria, but these are surprisingly unknown, despite the fact that they are important for the bacterium's survival and ability to infect. We therefore perform structural and functional research on these surface proteins. We have solved the crystal structures of all five proteins that make up one of these fimbria, the Mfa fimbria which is expressed by the periodontal pathogen Porphyromonas gingivalis. We now want to proceed to map its polymerization mechanism and the structure of the final fimbrial polymer. Since very little is known about the journey of fimbrial proteins from synthesis in the cytoplasm to mature polymer on the surface, we have chosen to study what happens in one of the first steps, when they are transported from the inner membrane to the outer.

The fimbrial proteins are labeled with a fatty acid and anchored in the inner membrane. The acyl-protein complex is recognized by a transport system, Lol, which transports the protein across the periplasm to the outer membrane. The transport system, which also carries other acyl-labeled proteins, is vital for all Gram-negative bacteria. The Lol system already serves as a target for the development of new antibacterial drugs and we therefore want to understand the structure and function of these proteins. Since the Lol system is not identical in proteobacteria and bacteroidetes, we use both Vibrio cholerae and P. gingivalis as model organisms.

In another project, we study a cytotoxin from V. cholerae. We have, together with collaborators, identified a toxin, MakA, which on its own can kill both nematodes, zebrafish and, surprisingly, some cancer cells. We have recently seen that MakA can form a tripartite complex with two other proteins, MakB and MakE, and together they are hemolytic, i. e. can make holes in certain host cells. We now want to investigate how MakA/B/E form this complex and how they selectively penetrate membranes. We perform all our studies with X-ray crystallography and/or electron microscopy, in combination with genetic and biophysical characterization. There is a great possibility that our research on bacteria from different phyla will provide knowledge that can also be applied to other pathogens.

More reading

Read more about our research at the Integrated Structural Biology website.

Head of research

Karina Persson
Associate professor
E-mail
Email

Overview

Participating departments and units at Umeå University

Department of Chemistry, Department of Molecular Biology

Research area

Chemical sciences, Infection biology