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Birte Vester

Birte Vester is Associate professor at Department of Biochemistry and Molecular Biology at the University of Southern Denmark. She obtained her Ph.d. from Department of Chemistry, Aarhus University in 1989 based on studies of antibiotic resistance and ribosomal RNA. After working as a clinical chemist in a few years she joined Stephen Douthwaites group at Department of Molecular Biology, Odense University. In 1993 she became Assistant professor at Department of Molecular Biology, Copenhagen University with her own independent research group studying RNA mutations and modifications and became Associate professor at the same depertment in 1997. In 2002 she returned to Odense and the University of Southern Denmark as an Assistant professor to work as part of the Nucleic Acid Centre. Her research has included interdisciplinary collaborations with various research groups, national (KU, DTU) as well as international (Germany, Sweden, Italy, Spain, Estonia). She is editor for Research in Microbiology and has participated in a number of committees for employment of professors, associate professors and post docs as well as international evaluations of research grants. She has been teaching at all levels at university, and supervising Ph.D. students, master project, and bachelor project.

Head of research: Associate professor Birte Vester

Research group:
Laboratory technician Lykke Haastrup Hansen

Antibiotics inhibiting protein synthesis and resistance mechansism

A main part of the research in the group deals with antibiotics inhibiting protein synthesis in bacteria and the corresponding resistance mechanisms. Many antibiotics function by binding to functional sites in the bacterial ribosome, where they block protein synthesis and thereby inhibit growth of bacteria. The increase in the appearance of bacterial resistance to many antibiotics underscores the importance of elucidating and understanding the mechanisms by which antibiotic act and how resistance occurs.

Current research projects 

Origin and dissemination of the enigmatic cfr antibiotic multi-resistance gene
We want to establish the origin and evolution of the cfr antibiotic resistance gene that was first found on a plasmid in Staphylococcus in year 2000. The gene codes for the enzyme Cfr that methylates ribosomal RNA at a specific position in the peptidyl transferase center and thereby provides resistance to six different classes of antibiotics. The gene is now found worldwide in clinic (especially in Staphylococcus) and in veterinary settings, but its origin and dissemination is unknown. By using sequence analysis, cloning and expression of various cfr look-alikes, by analysing antibiotic resistance and investigate methylations we will aim to answer at least some of the following questions; What is the origin of the gene and how is its related to the similar rlmN gene? Was it originally evolved to protect against antibiotics or does it also have some other function in bacteria or other organisms? What is its relation to other genes coding for radical SAM enzymes? How does it spread among bacteria?

Rational design of new antibiotics binding to bacterial ribosomes
The purpose is to develop new antibiotics that bind strongly and specifically to bacterial ribosomes. This includes antibiotics binding to ribosomes that are "resistant" due to mutations or methylations, which prevent binding of the existing antibiotics. This will be achieved by molecular modeling, synthesis, binding studies and growth inhibition studies, and this project is carried out as a close interdisciplinary cooperation between three research groups each specializing in their part. Many clinically relevant antibiotics bind to the ribosomal peptidyl transferase center (PTC) where amino acids are linked into proteins, and for a number of these antibiotics, crystal structures of ribosomal subunits with bound antibiotics are now known. Using this knowledge as a basis, we will develop derivatives of selected antibiotics that bind to PTC to create new interactions and improved binding affinity and aiming at circumvent resistance.

Do bacterial protein L3 mutations contribute to antibiotic resistance? 
This project focus on antibiotic resistance from mutations in ribosomal proteins. We believe that only a subset of the newly observed mutations are directly involved in antibiotic resistance but that they merely facilitate other resistance determinants or is related to some fitness matters. We examine this by constructing a vector suitable for expression of ribosomal proteins in E. coli knock-out strains where we remove the genome-coded ribosomal protein in question and force the bacteria to use the plasmid-coded version of the gene. We construct the relevant mutations on the plasmid-coded ribosomal protein genes and introduce them by swapping the plasmid carrying the mutation in question with the plasmid already present in E. coli. By measuring susceptibility to various antibiotics we can verify if the specific mutations are important resistance determinants or merely mutations appearing because of some other selection pressure. The project focuses on L3 and antibiotic resistance, but the methodology can be useful for other projects, also for other ribosomal proteins and other functional effects, e.g. fitness cost of ribosomal mutations.

Birte Vester is currently not accepting any project students.

Selected publications

Identification of 8-methyladenosine as the modification catalyzed by the radical SAMmethyltransferase Cfr that confers antibiotic resistance in bacteria
Giessing, A. N. B.; Jensen, S. S.; Rasmussen, A.; Hansen, L. H.; Gondela, A.; Long, K.; Vester, B.; Kirpekar, F., RNA, 2009, Vol. 15 (2), 327-336

The Cfr methyltransferase confers resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics
Long, K. S.; Poehlsgaard, J.; Kehrenberg, C.; Schwarz, S.; Vester, B.Antimicrobial Agents and Chemotherapy, 2060, Vol.50 (7), 2500-250

LNA (Locked Nucleic Acid): High Affinity Targeting of Complementary RNA and DNA
Vester, B.; Wengel, J., Biochemistry, 2004, Vol. 43 (42), 13233-13241

A full list of publications by associate professor Birte Vester can be found here.

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