Drug and antibiotic resistance
The rise of antibiotic-resistant bacterial strains in recent years has become one of the biggest known threats to humanity worldwide, leading to more than 700,000 deaths every year. As a result, the development of alternative strategies to prevent and treat infections is of paramount importance.
Bacterial adhesins: Bacterial adhesion is a key process in the early stages of infection and relies on specific interactions of bacterial cell wall molecules with receptors found on the surface of host cells. Based on the key role of bacterial adhesion in infectious diseases, the use of anti-adhesion compounds has been proposed as an alternative strategy in antimicrobial therapy.
Lysins as antibacterials: Bacteriophage endolysins (lysins) represent an attractive alternative class of antibacterials in the fight against infectious diseases. Lysins are phage-encoded peptidoglycan hydrolases which, when applied exogenously (as purified recombinant proteins) to Gram-positive bacteria, can result in rapid lysis and death of the bacterial cell.
Inhibitors of FosA: Fosfomycin, a broad-spectrum antibiotic, is used against various infections but the recent emergence of resistant strains against it threatens its clinical applications. FosA is a Mn2+- and K-dependent glutathione transferase that catalyzes the degradation of fosfomycin. The fosA gene is present in various Gram-negative bacteria, including Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens. Crystal structure determination and biochemical characterization of FosA complexes with ligands are employed to develop inhibitors of FosA.
Cancer drug resistance: Human glutathione transferases are a contributing factor to the development of drug resistance during cancer treatment. High-resolution structures, molecular docking, and molecular dynamics calculations are used to develop new compounds as inhibitors of the pi, mu, and alpha class of human glutathione transferases.
Multiple-herbicide resistance (MHR) is a global threat to weed control in cereal crops. In MHR weeds, a specific phi class glutathione transferase (MHR-GSTF) that confers resistance against multiple herbicides is expressed. We, therefore, aim to identify potent MHR-GSTF-inhibiting compounds derived from active pesticide databases in order to develop new strategies against MHR.
Development of molecular sensors
Glutathione transferases offer a versatile scaffold for manipulation to create new specificities and binding affinities. Using directed evolution techniques we aim to create engineered glutathione transferases for use as molecular sensors to detect pesticides and other hazardous compounds in the environment.
Streptococcus suis Dpr belongs to the Dps family of proteins that protect bacteria from oxidative stress. They form spherical 12-meric assemblies with a central cavity able to accommodate ~500 iron atoms as an iron core. We study the mechanism of the iron core formation using a variety of structural and molecular biology techniques. Understanding the mechanism of the iron core formation could lead to new nanoparticles with unique magnetic properties suitable for medical applications.
Protein stability for a sustainable future
The use of alternative fuels and utilisation of green chemistry processes have become key issues in sustainability discussions. Enzyme biocatalysis can play a critical role in the reduction of environmental pollution and the creation of better economic outcomes, leading to a more sustainable growth. Improved enzyme stability and efficiency are therefore important for the future of our planet. Enzymes from thermophilic fungi are being studied in an effort to understand better their thermostability and to find ways to improve them for better use in biotechnological applications.