Management of animal diseases and antimicrobial use by information and communication technology to control AMR in East Africa (MAD-tech-AMR)

In low-income countries (LICs), patterns of livestock diseases and antimicrobial use (AMU) are largely unknown, and there are few high-quality laboratory facilities. Robust and actor-centred surveillance systems are needed and surveillance of the dynamics leading to antimicrobial resistance (AMR) should precede more advanced systems.

Ongoing project

The project is designed to provide proof of concept, applying a framework for surveillance of: AMU, diseases that trigger AMU and perceived problems with AMR, in East African poultry production systems. Information and Communication Technology (ICT) will be coupled with veterinary epidemiology and social science methods. The originality lies in using frontline technology particularly suited for challenges in resource-poor settings. The overall objective is to provide an ICT framework for monitoring and control of AMU and AMR in livestock in LICs. The project will assess if veterinary “telemedicine” coupled with ICT systems can change AMU. Baseline data on AMU practices and actors involved will be collected, followed by a Knowledge-Attitudes-Practices study. A platform to register drug purchases and a database to monitor drug sales will be developed along with a mobile application for delivery of animal health advice and information about AMR. The ICT framework will be pilot-tested in selected poultry production systems in Kenya and Uganda. The framework can be expanded in the future to allow inclusion of diagnostic tools, but the initial focus is on clinical diagnosis based on tele-consultation and evidence-based therapeutic strategies.

Project partners

  • Susanna Sternberg Lewerin, Swedish University of Agricultural Sciences, Sweden (Coordinator)
  • Florence Mutua, International Livestock Research Institute, Kenya
  • Lawrence Mugisha, Makerere University, Uganda
  • Joshua Onono, University of Nairobi, Kenya

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Design, synthesis and lead generation of novel siderophore conjugates for the detection and treatment of infections by Gram-negative pathogens (SCAN)

There is a strong need for novel, innovative therapeutic solutions for infections caused by Gramnegative pathogens. In addition, there is a lack of tools to diagnose bacterial infections at deep body sites, e.g. on implant surfaces.

Ongoing project

In the project SCAN (Siderophore Conjugates Against Gram-Negatives), we apply a rational design approach to establish a targeting conjugate platform that can be used to both diagnose as well as treat bacterial infections (‘theranostics’ principle). The conjugates are actively transported into bacteria through their iron transport machinery that accepts siderophores as substrates.

This concept has recently been validated clinically and addresses a key issue of Gramnegative pathogens, the impaired translocation into the cell. We will design and synthesise novel siderophores that employ novel central scaffolds and combinations of iron-binding motifs. Those will be coupled with hitherto unexplored effectors: RNA polymerase inhibitors are employed as potent antibiotics, and dioxetane-based chemiluminescent probes will be used for imaging.

As a linkage between siderophore and antibiotic, cleavable, self-immolative linkers (e.g. trimethyl lock) will be constructed. The conjugates will be characterised in cellular assays and in infection models in mice. Their translocation and resistance mechanisms will be investigated by genetic and proteomic methods. The project should yield novel antibiotic lead structures with proven efficacy in vivo.

Project partners

  • Mark Brönstrup, Helmholtz Centre for Infection Research, Germany (Coordinator)
  • Doron Shabat, Tel-Aviv University, Israel
  • Isabelle Schalk, CNRS – Université de Strasbourg, France

Infections caused by multidrug-resistant Gram-negative bacteria result in significant mortality and morbidity worldwide. In line with this, all pathogens that received a ‘critical’ status by the recently established WHO priority list were drug-resistant Gram-negative species. The reasons for limited success of pharmaceutical research programs in the area of antibiotics have been carefully analyzed: the main hurdle is the limited understanding how to get drugs into Gram-negative bacteria. Thus, there is a strong need for novel, innovative drugs against infections caused by Gram-negative pathogens. There is also a lack of tools to diagnose bacterial infections at deep body sites, e.g. on implant surfaces.

In the project SCAN (Siderophore Conjugates Against gram-Negatives), we apply a rational design approach to establish a targeting conjugate platform that can be used to both diagnose and treat bacterial infections (‘theranostics’ principle). The conjugates are actively transported into bacteria through their iron transport machinery that accepts siderophores as substrates. As this resembles the strategy of ancient Trojan warriors, the approach has been named the ‘Trojan Horse Strategy’. This concept has recently been validated clinically, a first drug (Fetroja) has been approved and is available to patients.

We will design and synthesize artificial siderophores that employ novel central scaffolds and combinations of iron-binding motifs. Those will be coupled with hitherto unexplored effectors: RNA polymerase inhibitors are employed as potent antibiotics, and chemiluminescent probes will be used for imaging. As a linkage between siderophore and antibiotic, cleavable, self-immolative linkers will be constructed. The conjugates will be characterized in cellular assays and in animal infection models. Their translocation and resistance mechanisms will be investigated by genetic and proteomic methods.

The project should yield novel antibiotic lead structures as well as activatable bacterial probes with proven efficacy in vivo to detect and treat infections. Taken together, the afforded antimicrobials and moreover the novel theranostics could be tools that allow for strain-specific, potent treatment and monitoring of bacterial infections, addressing a major medical need expressed by the WHO.

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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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inCreasing cOmmunicatioN, awareNEss and data sharing in a global approaCh against resisTance (CONNECT)

The CONNECT network is based on the need for defining and implementing an integrated research strategy to facilitate the necessary studies and investigations for an innovative response to AMR. The CONNECT network output will contribute to the development of the JPIAMR-VRI by aligning stakeholders to share values on AMR with a One Health approach.

Completed project

The CONNECT network will provide an opportunity for stakeholders to consolidate around a common sets of goals, share their lesson learned and identify synergic work and effectively contribute to the collective impact of research. Recognising the complexity and scale of AMR is emphasised by the amount of resources needed to address the issue, and the limits of available resources and organisational capacities of governments, civil society, and philanthropy/charities.

Through partnerships, resources across sectors have the potential to complement one another and create more effective and sustained change. To have increased meaningful and sustainable impact, community engagement is needed. To develop trust, institutions and communities in the network should be involved in design and implementation of research. Developing member interoperability is expected to contribute to a strong and coherent globally connected effort based on exchange data, information, services and/or outputs, align their activities, policies and procedures and effectively operate together.

As an ultimate goal, the platform will encourage the development of priorities on strategic focuses, the engagement of brains thinking out of the box innovative solutions, and will represent the virtual and unique point for governing the research in Europe on the fight against AMR on a One Health approach.

Network partners

  • Nicola Petrosillo, National Institute for Infectious Diseases “Lazzaro Spallanzani”, IRCCS, Italy (Coordinator)

This network includes 20 partners, please click on the following link to see complete network composition: Network composition inCreasing cOmmunicatioN, awareNEss and data sharing in a global approaCh against resisTance (CONNECT)

Antimicrobial resistance (AMR) is one of the biggest public health challenges of our time. AMR is the ability of a microorganism to survive and grow in the presence of antimicrobial drugs, this phenomenon implies that antimicrobials are no longer effective to treat infectious diseases. The AMR problem is very complex and caused by multiple factors; an important cause is represented by the excessive use of antibiotics, not only in humans but also in food animal production and in agriculture. Addressing the growing threat of AMR requires a holistic and multidisciplinary approach – referred to as One Health – which includes all sectors such as hospitals, communities, farm animals, human and animal waste, wastewater systems.

To fight AMR, collaboration between researchers coming from different countries as well as from different scientific fields is essential. For this purpose, the JPIAMR established a virtual research institute (JPIAMR-VRI) with the main scope to improve visibility of the AMR research and facilitate knowledge exchange and capacity development across the globe, covering the full One Health spectrum. The CONNECT (inCreasing cOmmunicatioN, awareNEss and data sharing in a global approaCh against resistance) is one of the eight pillars that lay the foundation of the JPIAMR-VRI. In order to improve knowledge on AMR research and to allow findings sharing, and avoid duplication of research, the CONNECT network prepared a list of main projects and networks related to research on AMR in a One Health Approach. Moreover, links with other networks involved in the AMR research on a One Health approach were established, this will be the basis for a deeper cooperation between researchers across Europe and beyond and, importantly, for an exchange of findings and a sharing of research objectives with scientists working on animal health and on agricultural research.

Our network also prepared a proposal for a communication, dissemination and exploitation (CDE) plan to be used by all the VRI networks. The scope of this plan is to improve communication and dissemination of ideas on research projects and on the findings of projects. This is a tool that will allow to join efforts, minimize duplication and maximize potential of AMR research on a One Health approach. Moreover, the CDE plan will ensure that both the scientific community and the broad public understand the value of the JPIAMR –VRI and the importance of the One Health approach. In fact, to have meaningful and sustainable impact, community engagement is needed. The CONNECT network, along with the VRI networks, laid the foundation stone for developing scientists interoperability.

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Antimicrobial Resistance in Intensive Care (AMRIC)

The AMRIC (Antimicrobial Resistance in Intensive Care) network will use the InFACT infrastructure and collaboration network to spearhead a global acute care initiative for research on antimicrobial resistance.

Ongoing project

InFACT was established by independent investigator-led clinical research groups and academic research consortia to provide a mechanism to build international collaboration, address common needs, and to raise the profile of investigator-driven acute care research with researchers, policymakers, funders and the public. InFACT currently consists of 35 member networks representing every continent and income grouping on the planet and sharing the common goal to advance science and build research capacity. InFACT member networks are the leading research networks in critical care, with embedded mentoring and knowledge exchange activities. AMRIC, using the InFACT model and its pre-existing collaborations, will scale-up a plan for data sharing on the sources, burden, modifiable risk factors, and impact of antimicrobial resistance in acute care settings around the world. Through a recently funded and established mapping platform (ACCESS-MAPS, co-investigator Wallace) and a large team of motivated investigators, AMRIC will implement a plan for clinical and microbiologic data sharing for determining the scale of the AMR problem in acute care settings globally. The AMRIC network has recently conducted scoping reviews on the subject through prior JPIAMR support; this proposal will allow further planning for the implementation of the findings and coordinating the scaling-up of prospective data collection.

Network partners

  • Srinivas Murthy, University of British Columbia, Canada (Coordinator)

This network includes 22 partners, please click on the following link to see complete network composition: Network composition Antimicrobial Resistance in Intensive Care (AMRIC)

Call

Intensive Care Airway and Lung Microbiome Network ICALM Network (ICALM)

Hospital acquired pneumonia (HAP) is the most frequent infection acquired in the Intensive Care Unit (ICU). ICU-related respiratory infections arise as a consequence of the processes of ICU care. Mechanical ventilation (MV) is potentially lifesaving, but also carries microorganisms into the lower airways, changing the native flora, and increasing the risk of Ventilator-Associated Tracheobronchitis (VAT) and Ventilator-Associated Pneumonia (VAP).

Completed project

Data concerning the characteristics of respiratory microbiota and its alterations in illness are largely limited to the respiratory microbial flora of patients with cystic fibrosis, and little is known about airway microbiota alterations in critical illness. We published the most comprehensive study on this topic, and found that mechanical ventilation, but not antibiotic administration, was associated with changes in the respiratory microbiome.

With funding from JPIAMR, we will empower a multinational team to develop common surveillance methods and monitoring approaches to build a global study of the lung microbiome in critical illness, and its associations with modifiable environmental colonisation and pneumonia in the individual patient.

Network partners

  • Ignacio Martin-Loeches, Trinity College, Ireland (Coordinator)

This network includes 17 partners, please click on the following link to see complete network composition: Network composition Intensive Care Airway and Lung Microbiome Network ICALM Network (ICALM)


The current research needs a boost of open-source information to identify potential countries were healthcare problems are currently highly visible by government and non-government parties. The current network helped to become a tool for healthcare industry stakeholders in infection outbreaks for multi drug resistant pathogens. Stakeholders in the healthcare industry include customers/patients, employees/healthcare providers, creditors, shareholders and the government. The aim to have a multidisciplinary common field for primary stakeholders and end-users for the ICALM Network and members of InFACT networks. In addition, our findings were of relevance to translational research in critical care and clinical microbiologist, to public health decision-makers, and a partnership with academia and industry.

Our findings were disseminated using a twofold strategy:
– White paper on the scope of the problem under the JPIAMR acknowledgement, and the research agenda vision in the peer reviewed biomedical literature. Visibility was enhanced by publication in an open access journal such as Critical Care Journal
– World Federation of Societies of Intensive and Critical Care Medicine (the PI is part of the WFSICCM council), to present our awareness activities and meetings during the 2019 World Congress of Intensive and Critical Care Medicine in Melbourne Australia

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Wildlife, Agricultural soils, Water environments and antimicrobial resistance – what is known, needed and feasible for global Environmental Surveillance (WAWES)

The World Health Organisation (WHO), Food and Agriculture Organisation (FAO), and World organisation for Animal health (OIE), agree that surveillance of antibiotic/antimicrobial resistant bacteria (AMR) should be performed using a One Health multi-sectoral approach. Despite this, there is an overall lack of surveillance focusing on the environment and wildlife. Furthermore, there is unquestionably a lack of standardisation and synergy between projects and research efforts focusing on AMR in the environment and wildlife.

Completed project

The JPIAMR Strategic research agenda published in 2013 also highlighted the lack of data, comparable information and cross-sectoral studies on AMR in the environment. To amend this, we have initiated the WAWES network – Wildlife, Agricultural soils, Water environments and antimicrobial resistance – what is known, needed and feasible for global Environmental Surveillance, which consists of 27 partners from 16 countries from all over the globe representing low to high income settings.

The WAWES participants have a shared objective of finding a way to perform global comparative surveillance of AMR in the environment and wildlife, which is furthermore applicable in the majority of countries irrespective of economic resources. Due to the complexity of the environment WAWES will in the initial phase focus on wildlife, agricultural soils and water environments, including wastewater.

Network partners

  • Stefan Börjesson, National Veterinary Institute, Sweden (Coordinator)

This network includes 27 partners, please click on the following link to see complete network composition: Network composition Wildlife, Agricultural soils, Water environments and antimicrobial resistance – what is known, needed and feasible for global Environmental Surveillance (WAWES)

Antibiotic resistant bacteria (ARB) are one of the greatest challenges for both animal and human healthcare, this because the availability of antibiotics is the foundation for all modern medicine. To battle ARB surveillance plays an essential role to identify emergences of new or rare ARB, the continued transmission of more well-known ARB, and to assess if strategies and policies implemented to mitigate the spread has had an effect. In the endorsed action plans on antimicrobial resistance from The World Health Assembly (WHO), the Food and Agriculture Organization (FAO), and The World organization for Animal health (OIE) all agrees upon that surveillance should be performed in a one-health approach involving all sectors. Despite this, current national and international programs focus largely on the human and livestock sectors, in a limited number of countries companion animals is also included, but with the environment and wildlife generally overlooked. Furthermore, there is unquestionably a lack of standardization and synergy between projects and research efforts focusing on ABR in the environment and wildlife.

To amend this, we have initiated the WAWES network – “Wildlife, Agricultural soils, Water environments and antimicrobial resistance – what is known, needed and feasible for global Environmental Surveillance”, which consists of 27 partners from 16 countries from all over the globe representing low to high income settings. The WAWES participants have a shared objective of finding a way to perform global comparative surveillance of AMR in the environment and wildlife, which is furthermore applicable in most countries irrespective of economic resources. The work to focus on suggesting approaches to perform surveillance on ABR in the environment and wildlife is challenging mainly due to the complexity of the environment both on a macroscopic and microscopic scale, and the complexity of wildlife. In fact, one of the large hurdles, and the major ongoing discussion point of Wawes, is exactly defining what should be included in the definition of environment. Another major obstacle of suggesting approaches for surveillance on the environment and wildlife is that it preferably would be comparable to ongoing surveillance efforts in humans and livestock. However, the methods and chosen indicators for humans and livestock might not be suitable as indicators in the environment.

After initial discussions it was decided within Wawes to focus the efforts. First a white paper focusing on the suitability of using Escherichia coli, which is the major indicator bacteria for surveillance ARB efforts in human and livestock, as an indicator bacterium also in the environment. This work will define both the advantageous and primarily the weaknesses of using E. coli. In addition, the paper will also try to define the environment in the perspective of performing ABR surveillance. The second effort will be on an overview of ABR in wildlife with focus on other wildlife than birds since there already exist extensive studies and comprehensive reviews about ABR in wild birds. This work would also include on how wildlife should be defined in the perspective of performing ABR surveillance and highlight why wildlife is relevant when performing ABR surveillance.

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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.

Call

Predicting cell-cell horizontal transmission of antibiotics resistance from genome and phenome (TransPred)

Resistance to antibiotics, particularly in Gram-negative bacteria, is an accelerating health crisis. Only few new antibiotics against Gram-negatives are in clinical trials and resistance also to new antibiotics is predicted to spread rapidly upon clinical introduction.

Completed project

Horizontal transmission of antibiotic resistance factors within pathogenic species, combined with the selective pressure imposed by extensive antibiotic use that favours resistant strains, explains much of the accelerating antibiotics resistance crisis.

We propose to disclose candidate drug targets controlling the horizontal cell-cell transmission of anti-microbial resistance and to predict AMR and its transmission dynamics from bacterial genome composition. We employ experimental evolution of Escherichia coli, one of the most problematic species, to experimentally identify genes controlling the plasmid transmission rates. The hope is that these will be good targets for developing drugs that slows antibiotics resistance development. We also sequence the genomes of many clinical bacterial isolates and mathematically and computationally disclose natural variants likely to affect plasmid transmission properties.

We hope that this will lay the foundations for a future personalized medicine that tailors antibiotic choice to infection such that resistance development within each patient is delayed or avoided completely.

Project partners

  • Jonas Warringer, University of Gothenburg, Sweden (Coordinator)
  • Edward Moore, University of Gothenburg, Sweden
  • Gianni Liti, University of Nice, France
  • Danesh Moradigaravand, The Wellcome Trust Sanger Institute, United Kingdom
  • Jan Michiels, University of Leuven, Belgium
  • Anne Farewell, University of Gothenburg, Sweden
  • Ville Mustonen, The Wellcome Trust Sanger Institute, United Kingdom

Project resources

Tools

The manuscript that marks the release of the genomics and phenotypic resources and their global description is in preparation. Read more: github.com/matdechiara/TransPred

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A multi-scale approach to understanding the mechanisms of mobile DNA driven antimicrobial resistance transmission (JumpAR)

Antimicrobial resistance (AMR) is one of the greatest global health challenges. It spreads rapidly, constantly generating more dangerous bacteria.

Completed project

Mobile genetic elements (MGEs), segments of DNA that can move between bacterial cells, are a major route for resistance transfer in microbial communities. How often such ‘jumping genes’ move, which natural and man-made compounds influence them, and how they move at the molecular level is not understood.

In JumpAR, we surveyed MGEs in all bacteria, analysed their resistance cargos and transfer trends, and illuminated the molecular machinery that move them. Drawing on genome and metagenome sequences, we gained a global picture of the abundance and distribution of MGEs and revealed their profound impact on resistance transmission.

In a dedicated clinical study, we charted the effects of antibiotics on MGE-driven resistance spreading, and we identified human drugs and environmental compounds that can block AMR gene transfer in bacteria. We further delineated the structure and functioning of the molecular machinery, showing how MGEs build remarkably complex DNA shapes to promote insertion at diverse genomic sites, expanding gene transfer across diverse bacteria. Our collective results vastly expand knowledge on MGE-driven resistance spreading, opening doors to the development of novel strategies against resistance spreading.

JumpAR: Mechanism of AMR transmission

Project partners

  • Orsola Barabas, European Molecular Biology Laboratory, Germany (Coordinator)
  • Peer Bork, European Molecular Biology Laboratory, Germany
  • Maria Fällman, Umeå University, Sweden
  • Johan Normark, Norrlands University Hospital, Sweden
  • Gerard Wright, McMaster University, Canada

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