Antimicrobial resistance - network on chromosomally-mediated resistance

Antimicrobial resistance (AMR) is emerging as a major local and global threat to our health care system. Due to AMR, we are running out of effective therapy against infections. We have therefore built the unified network AMR-CHROM to support the development of innovative preventive and therapeutic measures along with novel diagnostics and drugs to combat AMR. In AMR-CHROM, we are mainly focusing on chromosomally mediated AMR in a One Health perspective, recognizing that the health of people is connected to the health of animals and the environment globally. AMR can be encoded by a plethora of genes and regulated by small RNAs and modified cellular functions. New drug resistance mechanisms are constantly evolving, and new genes and vectors of transmission are identified on a regular basis. In this context, we are focusing on chromosomally mediated resistance across the various sub-disciplines of microbiology, namely bacteriology, virology, mycology and parasitology. These chromosomal alterations are mediated by mutations that can induce changes in the structure of antibiotic targets, the modification or inactivation of antibiotics and the prevention of access to drug targets. In turn, AMR-CHROM has promoted novel drug targets as well as preventive and diagnostic measures. The AMR-CHROM partnership is formed by strong research groups with complementary and multidisciplinary expertise from all parts of Norway, teamed up with outstanding international collaborators. Critically, the network represents all sub-disciplines of microbiology, infectious diseases and infection biology in both human and veterinary medicine and agriculture. Thereby, both research-based innovation and integrated training on AMR have been secured.

The novel AMR-CHROM understanding of chromosomal mutations as an evolutionary driver in generating AMR represents a new strategy for the development of diagnostics, prevention and treatment of infections due to drug-resistant and multi drug-resistant microbes. Successful completion of our project has resulted in the development of innovative therapeutic strategies to combat AMR-related drug tolerance and resistance, diagnostics and vaccine candidates. We have established new successful interdisciplinary and international research collaborations. Dissemination of our results has opened up new avenues of preventive, diagnostic and therapeutic development towards combatting AMR in public health. The development of systematic AMR training and a new curriculum for bioinformatics courses relevant for a multitude of student and professional groups makes the outcome of AMR-CHROM sustainable for the future. Collectively, this will improve treatment outcomes and survival of AMR patients.

Antimicrobial resistance (AMR) is emerging as a major local and global threat to our modern health care system as we know it. Due to AMR, we are running out of effective therapy against infections. We hereby propose a unified net-working approach to support the development of innovative preventive and therapeutic measures along with development of novel diagnostics and drugs to combat AMR. In this context, we will mainly focus on chromosomally mediated AMR in a One health perspective, recognizing that the health of people is connected to the health of animals and the environment. The AMR-CHROM partnership is formed by strong research groups with complementary and multidisciplinary expertise from all parts of Norway, teamed up with outstanding international collaborators. Critically, the network represents all sub-disciplines of microbiology, infectious diseases and infection biology in both human and veterinary medicine, agriculture and the environment. Thereby, integrated training, research and innovation on AMR will be secured. AMR per se can be encoded by a plethora of genes and regulated by small RNAs and modified cellular functions. New resistance mechanisms are constantly being discovered, and new genes and vectors of transmission are identified on a regular basis. In this context, we will focus on chromosomally mediated resistance in the various sub-disciplines of microbiology, namely bacteriology, virology, mycology and parasitology. Chromosomally mediated resistance can be either naturally inherent resistance, mutations arising under reduced genome maintenance fidelity/defects in DNA repair, or mobile gene pools that are established chromosomally. These chromosomal alterations can induce changes in the structure and protection of antibiotic targets, the direct modification or inactivation of antibiotics and the prevention of access to drug targets. In turn, this delineation will reveal novel drug targets as well as preventive measures.