Antimicrobial resistance (AMR) is a global health threat, both in humans and animals. This situation has escalated globally and nationally in recent years, and has become one of the world's major pandemics. The World Health Organization (WHO) has generated a priority list of the most important global disease-causing microbes. We have therefore developed an INTPART strategy with research-based teaching and advanced research-based training to ensure innovative prevention, diagnostics and treatment to combat AMR.
The AMR-PART project focuses on the importance of antibiotic resistance with the bacteria Mycobacterium tuberculosis (Mtb) and Neisseria gonorrhoeae (Ng) as model organisms. Tuberculosis (TB) is one of the 10 deadliest diseases worldwide. The bacterium that causes TB is found in about 1/4 of the earth's population, and 10 million new TB cases are detected annually. The ongoing pandemic is exacerbated by antibiotic-resistant variants of the bacterium, so-called multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains. The WHO also reports 100 million cases of gonorrhea annually worldwide. To deal with these growing problems, we promote knowledge about and decipher how Mtb and Ng become resistant. Since antibiotics exert a selective pressure, hyper-mutating strains will occur during this form of stress, with selection of multi drug-resistant MDR and XDR strains.
The AMR project aims to 1) establish international cooperation for education, research and innovation, with the development of long-term AMR education programs; 2) to implement innovative learning in the analysis of large data sets, by promoting machine learning and artificial intelligence; and 3) to organize advanced courses and discover new intervention against multi-resistant microbes. We have therefore developed a set of advanced bioinformatics courses to promote efficient and deeper analysis of genome sequences, as a basis for machine learning to promote artificial intelligence. We have also conducted practical training to promote -Omics analyses. Not the least, we have in the network developed and exchanged completely new components and derivatives of recognized drugs, to develop new antibiotics. It turns out that modifications of macromolecules such as DNA, RNA and proteins have a lot to say for how antibiotics work and for how antibiotic resistance develops and is exerted.
Increased understanding of the mechanisms that make Mtb antibiotic resistant is essential to improve current TB treatment. In this context, we test the effect of new phenazine derivatives in drug-sensitive and resistant Mtb isolates. Our goal is to find out if the phenazine derivatives work in both reference strains and clinical Mtb isolates with different resistance patterns. The long-term goal is to discover the mechanism of how the phenazine derivatives work to fight Mtb infection (proof of concept). The effect of the phenazine derivatives has been analyzed by in vitro growth and detection of redox potential using Resazurin in microtiter assay (REMA). We have thus discovered that the phenazine derivatives work well against the clinical Mtb isolates with different forms of resistance. Thus, new and even better phenazine derivatives can also be developed. We aim to uncover mechanisms for the effect and development of Mtb resistance, and optimize the current version of TB treatment for new therapy that can be taken orally.
The INTPART AMR project is an interdisciplinary collaboration that connects researchers and students from different disciplines in a joint effort towards AMR. Top researchers from Norway (UiO), India (Indian Institute of Technology Indore), China (Zhejiang University and Nanshan CCDC Shenzen University) and South Africa (University of Cape Town) are project participants with active research, teaching and training. Three students have defended their Ph.D. in 2021. To the extent that the corona epidemic has allowed it during the project period, we have had exchanges of master and Ph.D. students. The goal is lasting human capacity building and technology transfer, also between industrial countries and low-income countries. This research-based teaching strategy for new diagnostics, prevention and treatment to combat AMR is in line with UN Sustainability Goals #3 (Good Health and Quality of Life), #4 (Good Education), #8 (Decent Work and Economic Growth), #9 (Industry, Innovation and Infrastructure) and #17 (Collaboration to achieve the Goals).
Antimicrobial resistance (AMR) is emerging as a major global threat to health care. The AMR challenge has escalated further the last 3 years. We propose a unified INTPART approach for research-based education in innovative preventive and therapeutic measures along with development of novel diagnostics to combat AMR. The AMR-PART partnership is formed by strong research groups in Norway with complementary and multidisciplinary expertise teamed up with outstanding international BRIC collaborators in South Africa, India, China and the US.
The AMR-PART project addresses the nature and role of chromosomally mediated antibiotic resistance with Mtb and Ng as model organisms. Tuberculosis affects 1/3 of the world's population. The incidence of AMR is still emerging as a public health problem worldwide. The AMR-PART project builds on the hypothesis that the current epidemics are fuelled by the selection of adapted and resistant microbial variants, due to antibiotic treatment. As antibiotics apply selective pressure, we postulate that hypermutating strains are likely to emerge, perpetuating the selection of multidrug-resistant and extensively drug-resistant strains. Consequently, components induced under antibiotics-stress will be investigated as potential drug targets. Mutant libraries will be constructed and component collections will be screened in combination with rational drug design to discover novel inhibitors. Hits identified will be characterized for their mechanism of action. Advanced courses, workshops and training will be established for each step of the experimental plan required to reach these goals. The expected outcome will be a pipeline of educational tools facilitating knowledge on AMR, in line with UN sustainable development goals # 3, 4, 8, 9 and 17. The research-based education will facilitate novel diagnostics, drug targets and drug leads over-riding AMR, as well as capacity building and frontline research-based education in sustainable settings.
