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NCCR AntiResist: New approaches to combat antibiotic-resistant bacteria

Umbrella Project
 | 
01.08.2020
 - 31.07.2032

Antibiotics are powerful and indispensable drugs to treat life threatening bacterial infections such as sepsis or pneumonia. Antibiotics also play a central role in many other areas of modern medicine, in particular to protect patients with compromised immunity during cancer therapies, transplantations or surgical interventions. These achievements are now at risk, with the fraction of bacterial pathogens that are resistant to one or more antibiotics steadily increasing. In addition, development of novel antimicrobials lags behind, suffering from inherently high attrition rates in particular for drug candidates against the most problematic Gram-negative bacteria. Together, these factors increasingly limit the options clinicians have for treating bacterial infections. The overarching goal of NCCR AntiResist is to elucidate the physiological properties of bacterial pathogens in infected human patients in order to find new ways of combatting superbugs. Among the many societal, economic, and scientific factors that impact on the development of alternative strategies for antibiotic discovery, our limited understanding of the physiology and heterogeneity of bacterial pathogens in patients ranks highly. Bacteria growing in tissues of patients experience environments very different from standard laboratory conditions, resulting in radically different microbial physiology and population heterogeneity compared to conditions generally used for antibacterial discovery. There is currently no systematic strategy to overcome this fundamental problem. This has resulted in: (i) suboptimal screens that identify new antibiotics, which do not target the special properties of bacteria growing within the patient; (ii) an inability to properly evaluate the efficacy of non-conventional antibacterial strategies; (iii) missed opportunities for entirely new treatment strategies. This NCCR utilizes patient samples from ongoing clinical studies and establishes a unique multidisciplinary network of clinicians, biologists, engineers, chemists, computational scientists and drug developers that will overcome this problem. We are excited to merge these disciplines in order to determine the properties of pathogens infecting patients, establish conditions in the lab that reproduce these properties and utilize these in-vitro models for antimicrobial discovery and development. In addition, clinical-trial networks and the pharmaceutical industry have major footprints in antimicrobial R&D. Exploiting synergies between these players has great potential for making transformative progress in this critical field of human health. This NCCR maintains active collaborations with Biotech SMEs and large pharmaceutical companies with the goal to: accelerate antibiotic discovery by providing relevant read-outs for early prioritization of compounds; enable innovative screens for non-canonical strategies such as anti-virulence inhibitors and immunomodulators; identify new antibacterial strategies that effectively combat bacteria either by targeting refractory subpopulations or by synergizing with bacterial stresses imposed by the patients' own immune system. This NCCR proposes a paradigm shift in antibiotic discovery by investigating the physiology of bacterial pathogens in human patients. This knowledge will be used to develop assays for molecular analyses and drug screening under relevant conditions and to accelerate antibacterial discovery, improve treatment regimens, and uncover novel targets for eradicating pathogens. Through this concerted effort, this NCCR will make a crucial and unique contribution to winning the race against superbugs.

Collaborations & Cooperations

2032 - Participation or Organization of Collaborations within own University
Basler, Marek, Prof., Biozentrum, Universität Basel, Research cooperation
2032 - Participation or Organization of Collaborations within own University
Bumann, Dirk, Prof., Biozentrum Universität Basel, Research cooperation
2032 - Participation or Organization of Collaborations within own University
Dehio, Christoph, Prof., Biozentrum, Universität Basel, Research cooperation
2032 - Participation or Organization of Collaborations within own University
Drescher, Knut, Prof., Biozentrum Universität Basel, Research cooperation
2032 - Participation or Organization of Collaborations within own University
Hiller, Sebastian, Prof., Biozentrum, Universität Basel, Research cooperation
2032 - Participation or Organization of Collaborations on a national level
Hierlemann, Andreas, Prof., D-BSSE, ETH Zürich, Basel, Research cooperation
2032 - Participation or Organization of Collaborations on a national level
Persat, Alexandre, Prof., Global Health, EPFL Lausanne, Research cooperation
2032 - Participation or Organization of Collaborations on a national level
Zampieri, Mattia, Prof., Institute of Molecular Systems Biology, ETHZ, Research cooperation
2024 - Participation or Organization of Collaborations within own University
Bumann, Dirk, Prof., University of Basel, Biozentrum, Research cooperation
2024 - Participation or Organization of Collaborations within own University
Drescher, Knut, Prof., University of Basel, Biozentrum, Research cooperation
2024 - Participation or Organization of Collaborations on a national level
Sarah, Tschudin Sutter, Prof. Dr. med., University Hospital Basel, Research cooperation
2024 - Participation or Organization of Collaborations on a national level
Sauer, Uwe, Prof., ETH Zürich, Research cooperation
2024 - Participation or Organization of Collaborations on an international level
Bickard, David, Prof., Institut Pasteur, Research cooperation
2024 - Participation or Organization of Collaborations on an international level
Moran-Gilad, Jacob, Prof., Ben-Gurion University of the Negev, Research cooperation
2024 - Participation or Organization of Collaborations on an international level
Rohn, Jenifer, Prof., University College London, Research cooperation

Funding

AntiResist: New approaches to combat antibiotic-resistant bacteria

NCCR Projekt Leading House Basel (GrantsTool), 08.2020-07.2032 (144)
PI : Bumann, Dirk,Dehio, Christoph,Jenal, Urs.
CI : Basler, Marek,Borgwardt, Karsten,Broz, Petr,Dittrich, Petra,Egli, Adrian,Harms, Alexander,Hiller, Sebastian,Khanna, Nina,Neher, Richard,Pieters, Jean,Rentsch Savoca, Katharina,Stolz, Daiana,Tschudin Sutter, Sarah,Zampieri, Mattia,van Nimwegen, Erik.

Publications

Sollier, Julie et al. (2024) ‘Revitalizing antibiotic discovery and development through in vitro modelling of in-patient conditions’, Nature Microbiology, 9(1), pp. 1–3. Available at: https://doi.org/10.1038/s41564-023-01566-w.

URLs
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Members (32)

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Dirk Bumann

Principal Investigator
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Christoph Dehio

Principal Investigator
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Urs Jenal

Principal Investigator
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Marek Basler

Co-Investigator
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Petr Broz

Co-Investigator
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Knut Drescher

Co-Investigator
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