Development of novel Mycobacterial Tolerance Inhibitors (MTIs) against MDR/XDR tuberculosis (MTI4MDR-TB)

In 2017, WHO published the Global Priority Pathogen lists with the aim to promote research and development of new treatments that are effective against microbes resistant to multiple antibiotics. Among them, multi- and extensively drug resistant Mycobacterium tuberculosis caused 48% of new tuberculosis (TB) cases in some countries in 2016.

Ongoing project

Current regimens for the treatment of TB include a combination of antibiotics developed for their strong efficacy against drug sensitive bacterium. The inadequacies of present TB therapies demand discovery of new agents with unique mechanisms of action to treat Mtb infection. Towards this end, we have discovered and developed a new family of ring-fused 2-pyridones (termed Mycobacterial Tolerance Inhibitors, MTIs) that potently sensitise Mtb to stresses encountered during infection and restores activity to the frontline antibiotic isoniazid (INH) in otherwise INH-resistant Mtb isolates.

Our short-term objectives are to demonstrate preclinical proof-of-concept for MTIs to combat Mtb infection, optimise the current lead MTIs for translation to a therapeutic, and reveal new insights into pathways of drug tolerance and resistance. Our long-term objective is to develop a new orally available antibiotic that improves the current regimens for patients with drug-resistant TB. We will also generate a deeper understanding of the MTI’s mode of action and their potential in synergistic interactions with other drugs. Importantly, we will also study how likely it will be for Mtb to develop resistance to combinations of MTIs and INH and other antibiotics.

Project partners

  • Fredrik Almqvist, Umeå University, Sweden (Coordinator)
  • Camille Locht, University of Lille, CNRS, Inserm, France
  • Tone Tønjum, University of Oslo, Norway
  • Jesús Blázquez, National Center for Biotechnology, CSIC, Spain
  • Christina Stallings, Washington University School of Medicine, USA

In 2017, WHO published the Global Priority Pathogen lists with the aim to promote research and development of new treatments that are effective against microbes resistant to multiple antibiotics. Among them, multi- and extensively drug resistant Mycobacterium tuberculosis caused 48% of new tuberculosis (TB) cases in some countries in 2016. Current regimens for the treatment of TB include a combination of antibiotics developed for their strong efficacy against drug sensitive bacterium. The inadequacies of present TB therapies demand discovery of new agents with unique mechanisms of action to treat Mtb infection. Towards this end, we have discovered and developed a new family of ring-fused 2-pyridones (termed Mycobacterial Tolerance Inhibitors, MTIs) that potently sensitise Mtb to stresses encountered during infection and restores activity to the frontline antibiotic isoniazid (INH) in otherwise INH-resistant Mtb isolates.

Our short-term objectives are to demonstrate preclinical proof-of-concept for MTIs to combat Mtb infection, optimise the current lead MTIs for translation to a therapeutic and reveal new insights into pathways of drug tolerance and resistance. Our long-term objective is to develop a new orally available antibiotic that improves the current regimens for patients with drug-resistant TB. We will also generate a deeper understanding of the MTI’s mode of action and their potential in synergistic interactions with other drugs. Importantly, we will also study how likely it will be for Mtb to develop resistance to combinations of MTIs and INH and other antibiotics.

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Flavodoxin inhibitors to kill resistant bacteria (FLAV4AMR)

This transnational collaboration gathers the expertise and resources required to address lead improvement to the point of producing novel antibiotics ready for clinical trials, and to clarify the overall importance of flavodoxin as a novel drug target.

Ongoing project

The project has two goals:

  1. To culminate the improvement of inhibitors of the flavodoxin from H. pylori, which have shown efficacy against reference and clinical strains (including a clarithromycin-resistant one) and in a mice model.
  2. To determine the relevance of flavodoxin as a novel drug target to fight bacteria which pose problems associated to antimicrobial resistance.

Project partners

  • Javier Sancho, Javier Sancho, Spain (Coordinator)
  • Eliette Touati, Pasteur Institute, France
  • Ultrich E Schaible, Research Center Borstel, Germany
  • Alain Bousquet-Melou, Ecole Nationale Vétérinaire de Toulouse, France

Some bacteria and other microorganisms are pathogens responsible for human infectious diseases. Bacterial infections are commonly fought using antibiotics or, more generally, antimicrobials. the prolonged use (and misuse) of antimicrobials over time to fight human infections has allowed some bacteria to develop molecular mechanism that neutralize antimicrobials. Such bacteria are in practice antimicrobial resistant and constitute a serious global threat to human health. In the European Union, antimicrobial resistance is responsible for 33,000 deaths annually and the costs of medical care and productivity losses are estimated in 1.5 billion euros.

The bacteria Helicobacter pylori (Hp) has been identified by the WHO as one of the pathogens for which it is urgent to find new antibacterial compounds, due to the high incidence of antibiotic-resistant strains along with the fact that half of the world’s population suffers from gastric infections caused by Hp, and because Hp infection constitutes a risk factor for developing gastric cancer. The Spanish-Franco-German project Flavodoxin inhibitors to kill resistant bacteria (FLAV4AMR), has been conceived as a transnational collaboration that brings together all expertise and resources needed to develop new antimicrobial compounds that could enter clinical testing and renew our arsenal against Hp. These novel antimicrobials act by a mechanism different from those of existing broad-range antimicrobials and therefore may be specific against Hp. Moreover they may not damage the beneficial microbiota and thus be useful for a personalize treatment of infectious diseases.

The project is led by Javier Sancho (Biochemistry Professor, and researcher at the University Institute for Research on Biocomputing and Physics of Complex Systems – BIFI). “Our ultimate goal is to develop new flavodoxin inhibitors having significant antimicrobial activity, both for Hp and for other pathogens that present significant problems because of their antibiotic resistance, and that can reach the market within a reasonable time, then, having a high impact on medicine,”

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Exploration of the TPP riboswitch as a new target for antibiotics (Explore)

In this project, we will explore the TPP riboswitch as a new drug target for antibiotics for key ESKAPE pathogens (E. coli, K. pneumoniae, A. baumannii, P. aeruginosa, S. aureus) and Streptococcus pneumoniae.

Ongoing project

The TPP riboswitch has already been validated as a drug target, however, potent and drug-like ligands with antibiotic activity are needed as starting points to develop novel strategies for anti-infective treatments. The goal of this proposal is to deliver such compounds. Using an innovative assay technology, we will develop a high-throughput assay that monitors simultaneously transcription efficiency and the regulatory activity of the riboswitch, which is crucial for its action, and use this assay to screen the CZ- and EU-OPENSCREEN libraries of lead-like compounds. The hits obtained will be thoroughly validated and the most promising hits will be optimised to improve their affinity.

The advanced compounds will be evaluated for antibiotic activity against the key ESKAPE pathogens and Streptococcus pneumoniae. We will also assess the broad-spectrum potential of the compounds and carry out mode of action studies to ensure that the compounds act on target. If the TPP riboswitch holds up to its high promises, this project will pave the way for urgently needed new antibiotics.

Project partners

  • Ruth Brenk, University of Bergen, Norway (Coordinator)
  • Petr Bartunek, Institute of Molecular Genetics of the ASCR, Czech Republic
  • Matthias Mack, Mannheim University of Applied Sciences, Germany
  • Gints Smits, Latvian Institute of Organic Synthesis, Latvia
  • Daniel Lafontaine, Université de Sherbrooke, Canada

The antibiotics we are currently using are losing effectiveness due to the emergence of resistant bacteria. Therefore, there is an urgent need to develop new antibiotics. In this project, we aim to develop ligands for an RNA element (a so-called riboswitch), that controls the expression of essential bacterial genes. These ligands can then serve as starting points for drug discovery for future antibiotics.

To reach this goal, we have assembled a team of highly skilled researchers from Norway, the Czech Republic, Latvia, Germany, and Canada. Together, we are developing a test system so that we can screen thousands of molecules for binding to the target. Subsequently, the identified ligands will be optimized to increase their affinity. The advanced compounds will be evaluated for antibiotic activity against the key bacteria for which new antibiotics are urgently needed. We will also carry out mode-of-action-studies to ensure that the compounds act on target as intended. If investigated riboswitch holds up to its high promises, this project will pave the way for urgently needed new antibiotics.

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Fighting antimicrobial resistant infections by high-throughput discovery of biofilm-disrupting agents and mechanisms (DISRUPT)

Many bacterial infections are associated with biofilms. Biofilm-related infections, particularly those caused by drug resistant bacteria, are difficult to handle with current antibiotic strategies. These includes wound-infections (e.g. caused by Pseudomonas aeruginosa or Staphylococcus aureus), urinary tract infections (e.g. Escherichia coli), chronic airway infections (e.g. P. aeruginosa) and preinfection colonisation by Streptococcus pneumoniae.

Ongoing project

New strategies and compounds to fight such resilient infections are imperative; however, the full repertoire of genes and processes that are essential for biofilm formation in different microbes is unknown. In this project, we aim to provide new tools, targets and agents for understanding and treating biofilm-associated infections in four major AMR pathogens (P. aeruginosa, UPEC, S. aureus and S. pneumoniae). To achieve this, we have assembled an interdisciplinary team with diverse expertise in microbial genetics and genomics, highthroughput screening and antibiotics/antibody research.

Our project involves a combination of stateof-the-art genetic approaches to construct genome-wide tools with automated biofilm-phenotyping and high-throughput screening for anti-biofilm antibodies and chemicals. Finally, we will characterise the mechanism of action of novel anti-biofilm agents.

Project partners

  • Morten Kjos, Norwegian University of Life Sciences, Norway (Coordinator)
  • Jan-Willem Veening, University of Lausanne, Switzerland
  • Athanasios Typas, European Molecular Biology Laboratory , Germany
  • Christoph Merten, European Molecular Biology Laboratory , Germany

Antimicrobial resistance is a growing problem worldwide. Many bacterial infections are nowadays often difficult to treat due to increasing antimicrobial resistance. Infections are particularly problematic if they are associated with biofilms. Biofilms are structured communities of bacteria, which are attached to surfaces. Infections typically caused by biofilms are wound-infections and urinary tract infections. The surface-attached biofilms are held together by a slimy matrix of polysaccharides, lipids, DNA and proteins. The matrix protects the bacterial cells against antibiotics and adds to the already existing resistance, making the infection treatment highly problematic. Novel strategies to treat such infections are therefore critical.

In our project we focus on four bacteria which has been listed as high-priority pathogens by WHO. These are (1) uropathogenic E. coli (the major cause of urinary tract infections and catheher infections), (2) Pseudomonas aeruginosa (whose biofilms are associated with chronic infections in wounds or during cystic fibrosis), (3) Staphylococcus aureus (causing biofilm-associated chronic wound – and medical implant infections), and (4) Streptococcus pneumoniae (whose biofilms have been associated with middle-ear infections and pneumoniae).

The DISRUPT project aims to identify new strategies to treat biofilm-associated infections. By inhibiting bacterial biofilms, the chances of infections will be reduced, and this will also resensitize the bacteria to existing antibiotics. To do this, we are using state-of-the-art genetic technologies (transposon sequencing, CRISPR interference) combined with high-throughput screens (screen for chemicals and microfluidic antibody screens) to identify anti-biofilm agents and mechanisms. The methods and resources we develop will be available for researchers worldwide, and will positively impact a range of research project related to AMR pathogens.

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Advancing CRISPR antimicrobials to combat the bacterial pathogen Klebsiella pneumoniae (CRISPRattacK)

The increasing incidence of multidrug-resistant bacterial infections and the trickling pipeline of novel antibiotic classes demand a new generation of antimicrobials. One promising avenue has been the development of antimicrobials based on CRISPR-Cas immune systems.

Ongoing project

These systems can be programmed to specifically and efficiently eliminate cells harbouring multi-drug resistance genes without impinging on resident microbiota. However, CRISPR antimicrobials remain to be advanced from a few proof-of-principle demonstrations to established therapeutics that can effectively combat the most pressing pathogens. Here, we propose to advance this antimicrobial platform to selectively kill Klebsiella pneumoniae, a major cause of multi-drug resistant, nosocomial infections worldwide.

We have devised a series of experimental approaches that will identify the most active CRISPR nucleases and DNA target sites for programmed killing, engineer bacteriophage delivery vehicles that can efficiently deliver CRISPR to a large fraction of clinical isolates, and evaluate the efficacy of the most promising therapeutic candidates in mouse infection models. Once demonstrated, the resulting optimised CRISPR antimicrobials will represent a large leap forward for the development of novel antimicrobials against Klebsiella, and they will provide a framework to develop similar antimicrobials against other high-priority pathogens associated with multidrug resistance.

Project partners

  • Chase Beisel, Helmholtz Centre for Infection Research, Germany (Coordinator)
  • Udi Qimron, Tel-Aviv University, Israel
  • David Bikard, Pasteur Institute, France
  • Sylvain Brisse, Pasteur Institute, France
  • Strowig Till, Helmholtz Centre for Infection Research, Germany

Multidrug-resistant bacterial infections are increasingly common, and the trickling pipeline of new antibiotics can do little to stem the tide. Instead, entirely new types of antibiotics are needed. One promising avenue involves CRISPR. CRISPR is best known for genome editing and a means to reverse genetic diseases. However, this same tool also be used to eliminate multidrug resistant pathogens while sparing commensal bacteria inhabiting our bodies. Early work highlighted the promise of these CRISPR antimicrobials, yet it remains a fledgling technology that requires further development before being ready for the clinic.

Through funding from JPIAMR, we are developing CRISPR antimicrobials against Klebsiella pneumoniae, a major cause of multidrug resistant infections worldwide. These pathogens often spread in hospitals and can be resistant to virtually every antibiotic at our disposal. Our goals are to deliver CRISPR to these bacteria using bacterial viruses called bacteriophages and ensure CRISPR can eliminate cells carrying antibiotic resistance. Toward this goal, we have assembled a team of experts in CRISPR biology and technologies, bacteriophage engineering, and Klebsiella. The team has been engineering bacteriophages as vehicles to deliver the CRISPR cargo to different Klebsiella strains found in hospitals. We have also been identifying the best CRISPR enzymes that eradicate cells with target sequences.

Finally, we are working toward experiments in mice that will lay a path toward clinical trials. The resulting optimized CRISPR antimicrobials will represent a leap forward toward the commercial development of novel antimicrobials against Klebsiella, and they will allow us to develop similar CRISPR antimicrobials against other multi-drug resistant pathogens. Through these efforts, we aim to provide new weapons against bacterial infections and turn the tide of antibiotic resistance.

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Anti-biofilm therapies using local application of bacteriophages (ANTIBIO-LAB)

The use of medical devices has had an enormously positive impact on patient care. However, approximately 5% of patients across all medical specialities can develop an infection associated with the device, which can have disastrous consequences.

Ongoing project

These bacterial infections involve biofilm formation and are therefore always highly antibiotic tolerant, even in the absence of specific antibiotic resistance genes. The antibiotic recalcitrance of the biofilm leads to poor treatment success rates and often requires implant removal to treat the infection.

The ANTIBIO-LAB consortium’s overall aim is to introduce a new concept in the treatment of antibiotic resistant biofilm infections by delivering biofilmadapted bacteriophages in a customised local delivery vehicle. The methods that we will employ draw from our collective experience in phage isolation, phage in vitro evolution, local delivery vehicle design, and clinically relevant in vitro and in vivo models of biofilm infection.

Project partners

  • Fintan Moriarty, AO Research Institute Davos, Switzerland (Coordinator)
  • Andrej Trampuz, Universitätsmedizin Berlin, Germany
  • Willem-Jan Metsemakers, University Hospitals Leuven, Belgium
  • David Eglin, AO Research Institute Davos, Switzerland
  • Rob Lavigne, Université Catholique de Louvain, Belgium
  • Mariagrazia Di Luca, PRO-IMPLANT Foundation, Germany

The use of medical implants has brought about an enormous progress in the care of patients. However, the development of bacterial biofilms adhered on the implant surface and the resulting resistance to antibiotics can lead to repeated infections. These infections lead to poor treatment success in all medical fields and very often, the implant has to be replaced. This project introduces a new concept for the treatment of antibiotic-resistant biofilm infections.

Content and goals of the research project: Bacteriophages are viruses that infect specifically bacterial cells and kill them within minutes to hours. Since bacteriophages require living bacteria to multiply, they cannot reproduce once the infection is eliminated. Therefore, bacteriophages are suitable for the natural and specific therapy of multi-antibiotic-resistant biofilm infections. The main goal of the project is to develop a suitable material for local administration of bacteriophages, which can be used for the treatment of antibiotic-resistant biofilm infections. Different methods and experiments for bacteriophage isolation and adaptation, as well as development of local administration materials and clinically relevant infection models are applied in this project.

Scientific and social context of the research project: The complementarity of the project partners offers a broad knowledge of essential clinical, microbiological and process technology. The project partners have already shown that bacteriophage therapy is an effective anti-infective therapy in the laboratory as well as in patients. Through the collaboration of all project partners, the effectiveness of bacteriophage therapy will be further enhanced by using the latest technologies in local administration materials. An effective therapy would have an enormous impact on the patient.

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VeRI BEAM

All recent reports establishing a roadmap to tackle the global, worldwide antimicrobial resistance (AMR) problem highlight the need to enlarge the current armamentarium beyond the sole “full antibiotic” model. Many efforts are being devoted to fulfil these needs both by academia and industry, as exemplified by the BEAM Alliance member portfolio (https://beam-alliance.eu/ba_pipeline). These new options include improved time-to-cure, anti-virulence, involvement of immune system, impact on flora, infection prevention, etc. both for animal and human medicine.

Completed project

However, while there is a clear path to Health Technology Assessment on antibiotic candidates (thanks to the EUCAST clinical breakpoint guidelines) no such established methodology is available for alternative antimicrobial treatments. Thus, any new treatment option faces the problem of lacking differentiation criteria to allow assessments of their products that do not have the possibility to be assessed by the classical MIC – PK/PD method. The clear definition of such criteria could benefit to the whole AMR research community. This uncertainty turns any such drug development into an undefined and risky market access condition. Consequently, private investors are reluctant to engage and to play a supporting role to pull-out promising candidates and bring them to the market. Most of the time, private companies learn or even co-build these requirements with (inter)national stakeholders, but this knowledge is rarely shared with e.g. academic labs or funding agencies, although it is of tremendous importance to anticipate pitfalls and avoid misuse of public funding.

The purpose of the VeRI BEAM Network is to implement a pilot action aiming at defining i) the above mentioned differentiation criteria and ii) the proper way to share the gained knowledge among AMR community. The pilot action will be used to validate a more general and long-term communication flow within the future JPIAMR-VRI between academic labs, and industrial and institutional actors in a non-competitive manner with a focus on innovative product development. Such a workflow will be helpful in anticipating R&D pitfalls and avoiding misuse of public funding.

For that purpose, the Network aims at:

  • Mapping the information needs both in terms of content and format expressed by academic and institutional actors;
  • Proposing an information workflow model;
  • Developing the differentiation criteria use case to challenge the foreseen model.

The proposed communication workflow model will ensure building capacity and strengthening capability of JPIAMR-VRI members through knowledge exchange mainly on the non-scientific side, but including business skills such as regulatory frameworks, manufacturing policies, marketing, technology or policy development. This can be part of a more general Training Plan to be implemented at the whole JPIAMR-VRI level. Finally yet importantly, the work focusing on the definition of new differentiation criteria is fully aligned with the goal of producing scientific evidence for developing policy and guidelines.

Network partners

  • Florence Séjourné, BEAM Alliance, France (Coordinator)

This network includes 26 partners, please click on the following link to see complete network composition: Network composition VeRI BEAM

When you get an infection, your doctor may give you an antibiotic. But on which ground is that specific pill being chosen to address your specific condition? It is sometimes quite difficult to choose between the different available antimicrobial drugs because they are basically compared on the basis of a single criterion: the required dose to kill or inhibit the pathogen measured in a specific (and sometimes irrelevant) experimental laboratory assay while the drug is being developed. In order to curb the AMR threat, innovators are now looking at the problem differently and are designing new approaches. Besides just killing the pathogen, drugs can exert other features that might be equally important such as the speed at which it kills the pathogen, the ability to circumvent existing resistance mechanism or pathogen-derived injuries to your organism, etc. But none of these features are being rigorously evaluated during the drug development and approval processes, because the regulatory pathways intended to validate the performance of all these new approaches are not ready.

The goal of our network was to highlight the need to develop new criteria to evaluate more comprehensively the different features exerted by an antimicrobial drug to enable an informed prescription, with the drug that is the most suited for your particular condition. Improving the differentiation of the AMR products would increase both their clinical value (to match the patient’s needs with the drug actions) and their market value (more benefits for the patient and the health system deserve a better price).

As a first step we defined a categorization framework allowing the identification of one or multiple medicinal activity for each drug. Then, we started discussing with the regulatory agencies to agree on the way to establish new criteria. We then focus on a particular category, regrouping microbes able to modulate their metabolism to become tolerant to the antimicrobials. Finally, we identified relevant assays to support the definition of appropriate evaluation criteria and designed a decision tree to help clinicians handle such medical cases.

The regulatory path to get new criteria accepted is a long way to go; but the work has been initiated and must be pursued to improve the way drugs are being developed and the valuable antimicrobials are prescribed.

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TRANSLOCATION-transfer (TT)

There is an urgent need for discovery and development of new drugs to combat multi-resistant organisms. The search for new drugs is cumbersome, particularly because the current business model for antibiotics in the pharmaceutical industry has been stalled because of the poor return on investment.

Ongoing project

In response to the pharmaceutical industry stepping back from antibiotic discovery, multiple public efforts, including the JPIAMR and IMI ND4BB, as well as the efforts of Biomedical Science (BMS) European Research Infrastructures community have stepped in to fill the gap. In this project, the TT network will set up a knowledge sharing network, Translocation-Transfer bringing together experts from with two major publically funded programs, with the goal to improve the process of academically driven antibiotic drug discovery by capitalising on recently gained insights into a key bottleneck in anti-bacterial research, namely how compound penetration properties determine efficacy and resistance properties.

Three existing communities forming the TT network are:
1) the partners associated with the multinational program Translocation (www.translocation.eu), part of IMI ND4BB;
2) partner sites from EU-OPENSCREEN, the European Research Infrastructure for chemical biology and screening (www.eu-openscreen.eu);
3) partners from the wider global community working on AMR issues and research.

Translocation (1/2013-6/2018) was one of the largest antibiotic research programs in the world specifically devoted to understanding and to devising ways of increasing antibiotic penetration into bacteria. EUOPENSCREEN began operations in April 2018 and from 2019 onwards will run some 50 chemical biology and academic drug discovery projects per year, across a network of 25 screening sites, based in eight European countries on behalf of users from across Europe. It is anticipated that at least 20% of EU-OPENSCREEN projects will involve antibiotic drug discovery element. The initial goal of the TT network will be to transfer knowledge between Translocation and EU-OPENSCREEN to fully incorporate compound permeation and efflux considerations into academic antibiotic drug discovery. We have the active participation of the Pew Charitable Trust, which will contribute to the long-term systematic dissemination of findings from the co-funded funded Translocation project to help academic antibiotic drug discovery efforts on a global scale.

Network partners

  • Mathias Winterhalter, Jacobs University Bremen, Germany (Coordinator)

This network includes 22 partners, please click on the following link to see complete network composition: Network composition TRANSLOCATION-transfer (TT)

Translocation-transfer aims to improve academically driven antibiotic drug discovery on a key bottleneck in anti-bacterial research, namely how compound penetration determine efficacy and resistance properties. There is an urgent need for discovery and development of new drugs to combat multi-resistant organisms. The search for new drugs is cumbersome, particularly because the current business model for antibiotics in the pharmaceutical industry has stalled because of the poor return on investment. In response to the pharmaceutical industry stepping back from antibiotic discovery, multiple public efforts, including the JPIAMR and IMI ND4BB, as well as the efforts of Biomedical Science (BMS) European Research Infrastructures community have stepped in to fill the gap. Translocation-transfer (TT) brings together experts from with two major publically funded programs, with the goal to improve the process of academically driven antibiotic drug discovery by capitalising on recently gained insights into a key bottleneck in anti-bacterial research, namely how compound penetration properties determine efficacy and resistance properties.

Three main communities form the TT network: i) the partners associated with the multinational program Translocation (www.translocation.eu), part of IMI ND4BB;ii) partner sites from EU-OPENSCREEN, the European Research Infrastructure for chemical biology and screening (www.eu-openscreen.eu) and iii) partners from the wider global community working on AMR issues and research.

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International Research Alliance for Antibiotic Discovery and Development (IRAADD)

The IRAADD network includes internationally renowned groups with excellent records of accomplishment in AMR research focussing on early stages of antibiotic discovery and development.

Ongoing project

This expert team will include natural products researchers, medical microbiologists, bioinformaticians, medicinal chemists and target-based drug designers, as well advisory partners from global alliances focussing on antibiotic development such as DNDi/GARDP and IMI-ENABLE. The partners of the network will set up a cooperative platform that will allow the sharing of scientific research data, translational knowledge and expert advice for the strategic development of new and advanced projects with the aim to take collaborative scientific research in the early stages of antibiotics discovery and development to a new level. IRAADD believes that such an integrative research network with international outreach will be an important step forward to close the gap in translational drug development, which has been lasting for several decades. IRAADD will represent a consortium of leaders from academia and other sectors who will actively address the worldwide concern of spreading AMR.

While this crisis is steadily expanding, research and development of novel antibiotics is inhibited because of underfinanced discovery and development projects prior to the preclinical trial phase, which are essential to provide new and innovative antibiotics for saving patient lives today and in future. In addition, there is currently no network available to leverage the ideas and projects of academic groups, which typically do not move forward towards application. Thus, our initiative aligns with the current “One Health Action Plan against Antimicrobial Resistance” introduced by the European Commission, which explicitly demands the implementation and support of “research into the development of new antimicrobials” and the establishment of sustainable research networks in this area. However, IRAADD strongly believes that the current situation and available institutions do not efficiently allow for a coordination and coaching especially of academic partners regarding translation of urgently required research on novel antibiotics into clinical use.

Network partners

  • Rolf Müller, Helmholtz Centre for Infection Research, Germany (Coordinator)

This network includes 37 partners, please click on the following link to see complete network composition: Network composition International Research Alliance for Antibiotic Discovery and Development (IRAADD)

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AMR Dx Global

AMR Dx Global is a transnational, multi-sectorial, multi-stakeholder and interdisciplinary network focussed on rapid diagnostics training and capacity building to tackle the global threat of antimicrobial resistance with a One Health approach. The network is coordinated by the University of Edinburg and brings together partners from 18 countries including international organisations like WHO, FIND, AMREF and ICAN.

Completed project

AMR Dx Global will develop a Strategic Action Plan on training to support the formation of the JPIAMR-VRI and focus on Diagnostics as one of the six priority topics of the JPIAMR Strategic Research Agenda. AMR Dx Global evolved from the successful JPIAMR Working Group AMR-RDT, which identified barriers to development, implementation and use of rapid diagnostics to tackle AMR. The findings of AMR-RDT has been published in Nature Reviews Microbiology and Lancet Infectious Diseases for publication. As before, AMR Dx Global has assembled an outstanding group of experts selected to match the scope of the JPIAMR VRI.

The new network provides exceptional access to and input from the leading national and international institutions, networks and activities in the field, which amplifies its immediate reach. Most importantly, the extensive coverage of existing global, international and national initiatives relevant to AMR, diagnostics, training, teaching and capacity building constitutes an exceptional opportunity for JPIAMR-VRI to receive input to its strategy and mitigate the risk of duplication amongst the many emerging transnational initiatives on AMR.

AMR Dx Global will run a twelve-month programme including two major meetings and structured data collection on existing strategies, needs and gaps in AMR diagnostics training and capacity building to develop the Strategic Action Plan on training for Diagnostics. The framework for AMR Dx Global and its ultimate vision is the set-up of a JPIAMR Virtual School of Diagnostics as part of the JPIAMR-VRI. Such Virtual School would create world-leading opportunity to connect the global AMR diagnostics community and stakeholders with the next generation of AMR scientists and turn the challenge of AMR into an opportunity for the next generation of researchers and the sustainable development goals.

Network partners

  • Till Bachmann, University of Edinburgh, United Kingdom (Coordinator)

This network includes 42 partners, please click on the following link to see complete network composition: Network composition AMR Dx Global

Diagnostics is one of the most important tools to tackle the global threat of antimicrobial resistance (AMR). AMR Dx Global is an international network with partners in 15 countries funded by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) as part of the emerging Virtual Research Institute (VRI) and coordinated by University of Edinburgh.

The network addresses the needs for teaching and training in relation to AMR diagnostics from a One Health perspective. The network conducted stakeholder mapping, content and delivery roadmapping as well as a demand survey for teaching and training on AMR diagnostics which includes for any type of diagnostics or test to provide information in the wider context of antibiotics, antibacterial resistance or infection such as tests for bacteria, antibiotic resistance genes, antibiotic susceptibilities, infection biomarkers, or antibiotic residues. The AMR Dx provides input into the formation of the JPIAMR VRI and recommends a strong presence of AMR diagnostics in the emerging platform.

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