Currently, the worldwide population is facing the post-antibiotic era, when most antibiotics will no longer be able to treat bacterial infections effectively. As introducing new antibiotics into clinical practice does not keep up with the development of resistance, adjuvant (combined) therapy appears to be a suitable alternative. We are interested in the identification of resistance mechanisms in clinical isolates of Staphylococcus aureus and their targeted inhibition using adjuvants. For this purpose, we are constructing a library of genetically modified Escherichia coli strains carrying a single resistance determinant. This determinant usually represents the gene for destructase, an enzyme that alters the structure of the antibiotic. E. coli strains prepared in this way have increased resistance to the action of the antibiotic. Subsequently, we will use these strains for high-throughput screening of the library of substances capable of reverting the antibiotic-resistant phenotype back to the sensitive one. Promising compounds will be subsequently tested for their ability to inhibit recombinant, purified destructase.
