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
- June 2019: Check out our new preprint on the autonomous role of bifunctional PBPs: Class A PBPs have a distinct and unique role in the construction of the pneumococcal cell wall.
- June 2019: Maria Victoria Heggenhougen started her PhD work in the group. She will work on CRISPRi in S. aureus. Welcome!
- June 2019: Maria and Malene defended their master thesis-work and finished their Master in Biotechnology. Congratulations!!
- April 2019: We have written about pneumococci in Aftenposten Viten.
- March 2019: Publication in mSphere together with the PEP-group: CRISPR Interference for rapid knockdown of essential cell cycle genes in Lactobacillus plantarum.
- March 2019: Paper published in Scientific Reports: Prevention of EloR/KhpA heterodimerization by introduction of site-specific amino acid substitutions renders the essential elongasome protein Pbp2b redundant in Streptococcus pneumoniae.
- March 2019: Contributed two chapter to the book "Streptococcus pneumoniae. Methods and protocols" (Methods in Molecular Biology), edited by Federico Iovino (Karolinska). The chapter were on construction of fluorescent proteins fusions and CRISPRi.
- January 2019: New paper in mBio: Structure of the Large Extracellular Loop of FtsX and Its Interaction with the Essential Peptidoglycan Hydrolase PcsB in Streptococcus pneumoniae. Preprint can be found here.
- December 2018: Project on a novel antibiotic funded by FRIMEDBIO.
- November 2018: New paper in PNAS by the NMBU Nitrogen Group: A bet-hedging strategy for denitrifying bacteria curtails their release of N2O, where we contributed.
- 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.
- September 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.
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 Victoria Heggenhougen, ph.d. student
Kjerstin Marita Ingvaldsen, master student