Birgitte H. Kallipolitis holds a position as Professor at the Department of Biochemistry and Molecular Biology, University of Southern Denmark. She obtained her Ph.D. in Molecular Biology in 1997 from the University of Southern Denmark. She was a postdoctoral fellow at the University of Copenhagen and a visiting scientist at UCC, Ireland. In 2001, she returned to the University of Southern Denmark as an Assistant Professor, and she became an Associate Professor in 2005. She was appointed Professor of Molecular Microbiology in 2017. The Kallipolitis-group has key competences in molecular studies of RNA and protein-based gene regulatory systems in gram-positive bacteria. The group manages a fully equipped biosafety level 2 lab at the Department of Biochemistry and Molecular Biology, including facilities for infection studies in cultured cell lines and the model host C. elegans.
Head of research: Professor Birgitte H. Kallipolitis
Guest researcher Janne Kudsk Klitgaard
Gene regualtory systems in pathogenic bacteria
The Kallipolitis group carries out research on gene regulatory systems in gram-positive bacterial pathogens, including Listeria monocytogenes and Staphylococcus aureus. We focus on understanding how RNA- and protein-based gene regulatory systems control the adaptation of bacterial pathogens to changing and stressful environmental conditions. We are particularly interested in uncovering the biological function and mechanism of action of small, regulatory RNAs. In addition, the nematode Caenorhabditis elegans is being exploited as a model host for the study of host-pathogen relationships. In other on-going research projects, we investigate new strategies for prevention and treatment of bacterial infections.
Current research projects
Exploring the role of regulatory sRNAs in bacterial pathogens
In this project, we are studying the cellular function and mechanism of action of small, regulatory RNAs (sRNAs) in pathogenic bacteria. By using two different approaches, we have identified several sRNAs in the gram-positive bacterial pathogens Listeria monocytogenes and Staphylococcus aureus. Our first approach, which also represents the first attempt ever to identify sRNAs in L. monocytogenes, resulted in the discovery of the Hfq-binding sRNAs LhrA, LhrB, and LhrC1-5. We have previously shown that the RNA-binding protein Hfq contributes to the stress tolerance and pathogenesis of L. monocytogenes in mice. In addition to the Hfq-binding sRNAs, we initiated a search for stress-inducible sRNAs in Staphylococcus aureus and L. monocytogenes, using a genome-wide bioinformatic screening approach. Having confirmed the presence of several sRNAs in these bacteria, the question to be answered is: What is their cellular function and mode of action? Considering the strategies employed for their identification, the sRNAs are most likely part of regulatory networks controlling stress- and virulence-associated genes. Our task now is to elucidate their exact physiological roles and mechanism of action. More specifically, we wish to identify the cellular targets (proteins or mRNAs) on which they act. For this purpose, we are using a range of experimental approaches to search for, validate and characterize the cellular targets of the sRNAs. We have shown that the sRNA LhrA is an Hfq-dependent trans-acting antisense RNA controlling the expression of multiple genes in L. monocytogenes, including the virulence-associated chitinase ChiA. LhrA represents the first example of an Hfq-dependent sRNA in Gram-positive bacteria. Furthermore, we have recently demonstrated that the multicopy sRNA LhrC controls the expression of the virulence adhesin LapB.
Reversal of antibiotic resistance by non-antibiotic helper compounds
The major goal of this research project is to elaborate knowledge for the development of new therapeutic strategies for the treatment of infections caused by antibiotic resistant microorganisms. Methicillin-resistant Staphylococcus aureus (MRSA) is a growing global problem and there is a shortage of new efficient drugs for the treatment of MRSA infections. Interestingly, it has been noticed that sensitivity towards traditional antibiotics can be restored by non-antibiotic helper compounds, i.e. therapeutic agents not originally designed for antibiotic purposes. The neuroleptic drug thioridazine has shown potential for therapeutic use in problematic infections caused by antibiotic resistant bacteria, such as MRSA. We investigate the molecular mechanisms underlying the restored sensitivity in microorganisms by non-antibiotic helper compounds using molecular genetics and biochemical methods. Furthermore, infections studies are performed by using mammalian cell lines and the nematode C. elegans as model host for S. aureus pathogenesis. This research project is part of an ongoing collaboration between the Kallipolitis group at BMB, SDU, and the research groups of Associate Professor Janne Kudsk Klitgaard and Professor H. J. Kolmos at the Department of Clinical Microbiology, Odense University Hospital.
A multicopy sRNA of Listeria monocytogenes regulates expression of the virulence adhesin LapB
Sievers, S., Sternkopf, E. M. S., Jacobsen, K., Lund, A., Mollerup, M. S., Nielsen, P. K., and Kallipolitis, B. H. Nucleic Acids Res., 2014, 42:9383-9398.
Defining a role for Hfq in Gram-positive bacteria: Evidence for Hfq-dependent antisense regulation in Listeria monocytogenes
Nielsen, J. S.; Lei, L. K.; Ebersbach, T.; Olsen, A. S.; Klitgaard, J. K.; Valentin-Hansen, P.; Kallipolitis, B. H., Nucleic Acids Res., 2010, 38: 907-919.
Thioridazine induces major changes in global gene expression and cell wall composition in methicillin-resistant Staphylococcus aureus USA300
Thorsing, M.; Klitgaard, J. K.; Atilano, M. L.; Skov, M. N.; Kolmos, H. J.; Filipe, S. R.; Kallipolitis, B. H., PLoS One, 2013, e64518
A full list of publications by associate professor Birgitte H. Kallipolitis can be found here.