Centre for new antibacterial strategies (CANS) is a new, large interdisciplinary centre at UiT – The Arctic University of Norway for research, education, innovation and dissemination related to antimicrobial resistance (AMR). CANS currently involves fourteen research groups located at three faculties and covers topics within marine bioprospecting – identification and characterization of new antibacterial activities, design and synthesis of new antibiotics and resistance inhibitors, the evolution and molecular epidemiology of AMR, host-microbe-drug interactions as well as antibiotic stewardship. The centre aims to strengthen current activities, but also support new basic research in novel concepts for sustainable antibacterial activities in AMR-prevention and treatment strategies through new permanent and temporary (tenure-track, postdoc and PhD) positions.
The major interest is the design and synthesis of antibiotic resistance breakers – new molecular solutions to the AMR challenge. Our focus is on carbapenemase inhibitors and membrane-active small molecules. In collaboration with the LacZyme group and international collaborators, we have a unique program in fragment- and structure-based molecular design of carbapenemase inhibitors. Moreover, we have experience in natural-product synthesis and are involved in a series of natural-product based drug discovery projects focusing on anti-bacterial compounds in collaboration with other CANS-related groups.
Synthetic organic chemistry, asymmetric synthesis, absolute configuration, natural products, peptide synthesis, NMR, mass spectrometry, medicinal chemistry, antimicrobial compounds, drug design, quantitative structure-activity relationships.
Focused interests on drug delivery systems as means for improved drug bioavailability and therapeutic outcome. The group aims at gaining a deeper understanding of transport processes of drugs and drug delivery systems destined for oral, parenteral and topical route of drug administration, enabling improved therapeutic drug effects and reduced toxic effects by increasing the drug targeting. Specific focus on localized treatment of skin and vaginal infections, thereof reducing the systemic exposure to antimicrobial substances. In addition, delivery of natural origin and novel antimicrobials are the pipelines in current research.
HMI searches novel and innovative bacterial targets for future infection prevention and treatment. We perform multilevel (resistance gene, mobile genetic element, clone) molecular epidemiological studies of antimicrobial resistance and colonization/infection determinants in important human pathogens including S. aureus, E. faecium/faecalis and Klebsiella pneumoniae. The relevant targets are tested in molecular and functional assays as well as in animal infection models. In addition, we explore the use of genomics in rapid diagnostic microbiology and contribute with MIC- and mode of action assays in antimicrobial drug discovery projects.
Pharmacoepidemiology – Population level use of antimicrobials. Antimicrobial use among related to birth season. Predicting antimicrobial at municipality level using machine learning, socioeconomic and demographic factors. Consumption of antimicrobials during travel. Clinical pharmacy – Hospital treatment of community acquired pneumonia.
K-res is the national reference laboratory for carbapenemase-producing and colistin resistant Gram-negative bacteria (Enterobacterales, Acinetobacter spp., and Pseudomonas spp.) as well as linezolid resistant and vankomycin resistant enterococci. Our current research activities include: (i) Evaluations of diagnostic methods for detection of antimicrobial resistance. (ii) Multilevel molecular epidemiology studies of antimicrobial resistant human pathogens (resistance genes, mobile genetic elements and clones) including Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae in national and international networks. (iii) Prevalence of antimicrobial resistance in healthy carriers (Tromsø 7 population study). (iv) Elucidation of novel resistance mechanisms, evolutionary aspects and transmission dynamics of antimicrobial resistant pathogenic clones. (v) Search for novel anti-virulence targets for infection prevention/treatment and inhibitors for carbapenemases. (vi) Investigations of membrane vesicles as vehicles for communication with bacteria and eukaryotic cells and possible vaccine against multidrug resistant E. faecium. K-res is an ESCMID Collaborative Centre and a EUCAST Antimicrobial Susceptibility Testing Network Laboratory.
The LacZymes group focuses on ß-lactamases, enzymes breaking down ß-lactam antibiotics and deactivating their antibacterial properties. The ß-lactam antibiotics have long been a cornerstone for the treatment of bacterial diseases, but worryingly many bacteria are now resistant to these drugs. The most common resistance mechanism towards ß-lactam antibiotic is the production of ß-lactamases, and transferable ß-lactamases-encoding genes is spreading rapidly dramatically limiting treatment options. ß-lactamases include both metallo-ß-lactamases (MBLs) and serine-ß-lactamases (SBLs), and occur mainly in Gram-negative pathogens including Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii. Our long-term goal is finding new inhibitors for both ß-lactamase classes, to be used in combination with a ß-lactam to prolong their lifetime. The group of ß-lactam antibiotics includes penicillins, cephalosporins and carbapenems.
Marbio's focus is discovery of bioactive compounds from marine organisms. The main activities are screening crude extracts/fractions for different bioactivities and performing bioassay-guided purification to isolate active compounds and hence build up a library of natural products. We explore Arctic and sub-Arctic marine organisms, searching for compounds with activities against bacteria, cancer and diabetes as well as compounds with immunomodulatory and antioxidative effects.
The group focus on drug discovery and bioprospecting on natural products and particularly basic knowledge of marine antimicrobials, their structures and mechanisms of actions towards bacteria or biofilms.
Microbial evolution: Evolution, selection and spread of antimicrobial resistance; selection inversion strategies for alternative use of antimicrobials; horizontal gene transfer.
Targeted inhibition of virulence factors in general is recognized as a promising approach against infectious diseases. Pathogens confronted with such compounds, will have a reduced ability to evade clearance by the human immune responses and will be hampered establishing an infection. When used as adjuvants, reduced amounts of classical, small-molecule antibiotics might be necessary to achieve efficient infection treatment.
Several human pathogenic bacteria produce and secrete toxic zinc metalloproteases, the most prominent examples being pseudolysin, aeruginolysin (both Pseudomonas aeruginosa), vibriolysin (Vibroio sp.), aureolysin (Staphylococcus aureus) and thermolysin (Leptospira). These extracellular virulence factors are central during the infection processes and are known to degrade human tissue components and components of the human immune system. We are using a combination of different molecular modelling methods (docking and scoring, ligand-based and target-based virtual screening, molecular dynamics simulations) and inhibition kinetics to study molecular mechanism and inhibition of bacterial and human zinc metalloproteinases. Our aim is to identify selective inhibitors of the bacterial virulence factors that do not interfere with human zinc metalloproteinases.
Design and synthesis of peptides, peptidomimetics and marine natural product mimics (MNPMs) with activity against multidrug resistant (MDR) bacteria and compounds with antibiofilm activity. The group has also research projects within the fields of proteomics, metabolomics and pharmaceutical analytical chemistry.
Surveillance of antimicrobial resistance in human pathogenic bacteria in a One Health perspective. Molecular epidemiology of antimicrobial resistance in human pathogenic bacteria. Public health burden of antimicrobial resistance. Usage of antibiotics in clinical practice. The role of hospital infection control in containment of antimicrobial resistance. Epidemiology of bacterial colonization in population-based cohort studies.
The group current focus is on antibiotic resistance among oral streptococci mediated by mobile genetic elements like Tn916/Tn1545 family and the fitness cost of these elements in streptococci. Research on proper use of antibiotics in dental practice is another topic.
Infections and antibiotics to neonates. We are collaborating with the Norwegian Neonatal Network and a network of European neonatologists. By using high quality, population based epidemiological data we aim to improve therapy for vulnerable neonates. We also perform own studies on long term follow up of side effects (gut problems, antibiotic resistance and ototoxicity).
Gut microbiota of preterm infants and in children with HIV
We aim to detect the impact of antibiotic and probiotic treatment, in different pediatric populations. In children with HIV we are specifically studying the effect of azithromycin given to prevent respiratory problems in HIV-positive African children. In preterm infants, the effects of probiotics are of great interest as probiotics are increasingly used in order to prevent gut inflammation and avoid antibiotic resistance development.