CARTNET has addressed the challenge of antimicrobial resistance in bacterial pathogens that can be transmitted between humans and animals including methicillin resistant Staphylococcus aureus (MRSA) and pathogenic E. coli. For these pathogens, resistance is becoming critical as less and less treatment options are available while at the same time multidrug resistance is becoming more frequent. In consequence society is increasingly needing options for antimicrobial therapy not just for treating human infections but also for reducing the pool of resistant bacterial pathogens in animals, such as livestock, from which antibiotic resistance may be transmitted. The project aimed to develop alternative solutions approaches and compounds to target antibiotic resistant pathogens and did so by investigating phage therapy to target pathogenic E. coli in poultry; by limiting the spread of phages needed by livestock MRSA for human infections; by developing new antimicrobials that target essential signal transduction systems and by exploring novel antimicrobials expressed from the environmental organisms. These objectives were addressed by structure guided improvement of small molecule inhibitors, by eliciting expression of silent antimicrobial gene clusters in genera of actinomycetes and based, by metagenomic data as well as screenings identify novel compounds in various habitats, by isolating phages to be used in phage therapy and by identifying intrinsic and transferable antibiotic resistance mechanisms that could guide identification of risk markers pointing to strains prone to resistance development.
