We study different molecular mechanisms relevant for understanding antibiotic resistance and for identification of novel antimicrobial target sites in pneumococci (pneumokokker, S. pneumoniae) and staphylococci (stafylokokker, S. aureus). These pathogens are responsible for millions of deaths worldwide every year and treatment of infections are increasingly problematic due to the emergence and spread of antibiotic resistance (including penicillin-resistant S. pneumoniae and methicillin-resistant S. aureus, MRSA).
News & new publications
- October 2018: New preprint - Prevention of EloR/KhpA heterodimerization by introduction of site-specific amino acid substitutions renders the essential elongasome protein PBP2b redundant in Streptococcus pneumoniae
- October 2018: New preprint - Structure of the large extracellular loop of FtsX and its interaction with the essential peptidoglycan hydrolase PcsB in Streptococcus pneumoniae.
- Sept 2018: Marte will join our group for some months to work on staphylococci and antibiotic resistance.
- August 2018: Maria, Malene and Kjerstin started their master projects and Janne her bachelor project in the group. Welcome!
- August 2018: New paper in Nature Communications - Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae.
- June 2018: Silje and Catharina successfully finished their master projects and degrees. Congratulations!
- June 2018: Nascent teichoic acids insertion into the cell wall directs the localization and activity of the major pneumococcal autolysin LytA, published in The Cell Surface.
Main research topics
Bacterial transformation and quorum sensing
Transformation by horizontal gene transfer has been an underestimated factor in the evolution of life on earth. For example, the rapid emergence of penicillin resistance among pneumococcal strains is due to their natural ability to become competent for natural transformation, i.e. to take up naked DNA from the environment. This property enables pneumococci to exchange genes with their siblings or members of closely related species. To be able to control the spread of antibiotic resistance and other virulence genes it is important to understand how natural transformation contributes to the dissemination of these genes.
Natural transformation in pneumococci also represents a prominent example of quorum sensing based gene regulation, where bacteria communicate via export of small peptide pheromones. The group aims at understand the molecular details of such quorum sensing based gene regultaion and eventually be able to control such mechanisms.
Penicillin resistance and cell wall synthesis in Streptococcus pneumoniae
The cellular targets of penicillins are the so called penicillin-binding proteins (PBPs). Alterations in these enzymes that reduce their affinity for penicillins have been recognized as the major penicillin-resistance mechanism operating in S. pneumoniae. The normal function of PBPs is to synthesize the pneumococcal cell wall (the peptidoglycan sacculus). Although the reactions catalyzed by the pneumococcal PBPs are well known, there are several aspects related to PBPs which are poorly understood. We are therefore studying (i) the specific role of each PBP in synthesizing and shaping the peptidoglycan sacculus, (ii) regulation of PBP activity (iii) interaction between PBPs and other proteins, (iv) sub-cellular localization of PBPs and the activities of low-affinity PBPs.
The cell cycle of Staphylococcus aureus
Many antibiotics are targeting essential processes of the bacterial cell cycle, including DNA replication, cell wall synthesis and cell division. Using different genetics and biochemistry approaches, we aim to identify novel factors involved in the staphylococcal cell cycle, which can serve as target sites for antimicrobials.
Maria Heggenhougen, master student
Malene T. Nesdal, master student
Kjerstin Marita Ingvaldsen, master student