Towards the sustainable discovery and development of new antibiotics

Marcus Miethke; Marco Pieroni; Tilmann Weber; Mark Brönstrup; Peter Hammann; Ludovic Halby; Paola B. Arimondo; Philippe Glaser; Bertrand Aigle; Helge B. Bode; Rui Moreira; Yanyan Li; Andriy Luzhetskyy; Marnix H. Medema; Jean Luc Pernodet; Marc Stadler; José Rubén Tormo; Olga Genilloud; Andrew W. Truman; Kira J. Weissman; Eriko Takano; Stefano Sabatini; Evi Stegmann; Heike Brötz-Oesterhelt; Wolfgang Wohlleben; Myriam Seemann; Martin Empting; Anna K.H. Hirsch; Brigitta Loretz; Claus Michael Lehr; Alexander Titz; Jennifer Herrmann; Timo Jaeger; Silke Alt; Thomas Hesterkamp; Mathias Winterhalter; Andrea Schiefer; Kenneth Pfarr; Achim Hoerauf; Heather Graz; Michael Graz; Mika Lindvall; Savithri Ramurthy; Anders Karlén; Maarten van Dongen; Hrvoje Petkovic; Andreas Keller; Frédéric Peyrane; Stefano Donadio; Laurent Fraisse; Laura J.V. Piddock; Ian H. Gilbert; Heinz E. Moser; Rolf Müller

doi:10.1038/s41570-021-00313-1

Towards the sustainable discovery and development of new antibiotics

Marcus Miethke, Marco Pieroni, Tilmann Weber, Mark Brönstrup, Peter Hammann, Ludovic Halby, Paola B. Arimondo, Philippe Glaser, Bertrand Aigle, Helge B. Bode, Rui Moreira, Yanyan Li, Andriy Luzhetskyy, Marnix H. Medema, Jean Luc Pernodet, Marc Stadler, José Rubén Tormo, Olga Genilloud, Andrew W. Truman, Kira J. WeissmanEriko Takano, Stefano Sabatini, Evi Stegmann, Heike Brötz-Oesterhelt, Wolfgang Wohlleben, Myriam Seemann, Martin Empting, Anna K.H. Hirsch, Brigitta Loretz, Claus Michael Lehr, Alexander Titz, Jennifer Herrmann, Timo Jaeger, Silke Alt, Thomas Hesterkamp, Mathias Winterhalter, Andrea Schiefer, Kenneth Pfarr, Achim Hoerauf, Heather Graz, Michael Graz, Mika Lindvall, Savithri Ramurthy, Anders Karlén, Maarten van Dongen, Hrvoje Petkovic, Andreas Keller, Frédéric Peyrane, Stefano Donadio, Laurent Fraisse, Laura J.V. Piddock, Ian H. Gilbert, Heinz E. Moser^*, Rolf Müller^*

^*Corresponding author for this work

Research output: Contribution to journal › Review › peer-review

Abstract

An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.

Original language	English
Journal	Nature Reviews Chemistry
Volume	5
Pages (from-to)	726-749
ISSN	2397-3358
DOIs	https://doi.org/10.1038/s41570-021-00313-1
Publication status	Published - 2021

Bibliographical note

Funding Information:
We are grateful to Édith Brochu (JPIAMR-VRI, Canada) for helpful discussion and comments during manuscript preparation. Coordination of the IRAADD consortium is funded by the JPIAMR-VRI, including the publication of this article. The project on PqsR pathoblocker development acknowledges funding through the German Center for Infection Research (DZIF; projects TTU09.908 and TTU09.916), the Helmholtz Association (Helmholtz Validation Fund) and additional contributions by the associated academic institutes (HZI and HIPS). The development of chelocardins is supported by the DZIF (TTU09.814/09.821), the Helmholtz Innovation Fund (Pre-4D), by the Slovenian Research Agency, ARRS, grant no. J4-8226, and in collaboration with AciesBio, Slovenia. The corallopyronin project is funded by the DZIF (TTU09.807/09.816, TTU09.914), the German Federal Ministry of Education and Research (BMBF), the federal state of North Rhine-Westphalia (EFRE.NRW) and EU Horizon 2020. Eriko Takano was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 720793 “TOPCAPI: Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients”.

Publisher Copyright:
© 2021, Springer Nature Limited.

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Miethke, M., Pieroni, M., Weber, T., Brönstrup, M., Hammann, P., Halby, L., Arimondo, P. B., Glaser, P., Aigle, B., Bode, H. B., Moreira, R., Li, Y., Luzhetskyy, A., Medema, M. H., Pernodet, J. L., Stadler, M., Tormo, J. R., Genilloud, O., Truman, A. W., ... Müller, R. (2021). Towards the sustainable discovery and development of new antibiotics. Nature Reviews Chemistry, 5, 726-749. https://doi.org/10.1038/s41570-021-00313-1

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abstract = "An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.",

author = "Marcus Miethke and Marco Pieroni and Tilmann Weber and Mark Br{\"o}nstrup and Peter Hammann and Ludovic Halby and Arimondo, {Paola B.} and Philippe Glaser and Bertrand Aigle and Bode, {Helge B.} and Rui Moreira and Yanyan Li and Andriy Luzhetskyy and Medema, {Marnix H.} and Pernodet, {Jean Luc} and Marc Stadler and Tormo, {Jos{\'e} Rub{\'e}n} and Olga Genilloud and Truman, {Andrew W.} and Weissman, {Kira J.} and Eriko Takano and Stefano Sabatini and Evi Stegmann and Heike Br{\"o}tz-Oesterhelt and Wolfgang Wohlleben and Myriam Seemann and Martin Empting and Hirsch, {Anna K.H.} and Brigitta Loretz and Lehr, {Claus Michael} and Alexander Titz and Jennifer Herrmann and Timo Jaeger and Silke Alt and Thomas Hesterkamp and Mathias Winterhalter and Andrea Schiefer and Kenneth Pfarr and Achim Hoerauf and Heather Graz and Michael Graz and Mika Lindvall and Savithri Ramurthy and Anders Karl{\'e}n and {van Dongen}, Maarten and Hrvoje Petkovic and Andreas Keller and Fr{\'e}d{\'e}ric Peyrane and Stefano Donadio and Laurent Fraisse and Piddock, {Laura J.V.} and Gilbert, {Ian H.} and Moser, {Heinz E.} and Rolf M{\"u}ller",

note = "Funding Information: We are grateful to {\'E}dith Brochu (JPIAMR-VRI, Canada) for helpful discussion and comments during manuscript preparation. Coordination of the IRAADD consortium is funded by the JPIAMR-VRI, including the publication of this article. The project on PqsR pathoblocker development acknowledges funding through the German Center for Infection Research (DZIF; projects TTU09.908 and TTU09.916), the Helmholtz Association (Helmholtz Validation Fund) and additional contributions by the associated academic institutes (HZI and HIPS). The development of chelocardins is supported by the DZIF (TTU09.814/09.821), the Helmholtz Innovation Fund (Pre-4D), by the Slovenian Research Agency, ARRS, grant no. J4-8226, and in collaboration with AciesBio, Slovenia. The corallopyronin project is funded by the DZIF (TTU09.807/09.816, TTU09.914), the German Federal Ministry of Education and Research (BMBF), the federal state of North Rhine-Westphalia (EFRE.NRW) and EU Horizon 2020. Eriko Takano was funded by the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement no. 720793 “TOPCAPI: Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients”. Publisher Copyright: {\textcopyright} 2021, Springer Nature Limited.",

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Miethke, M, Pieroni, M, Weber, T, Brönstrup, M, Hammann, P, Halby, L, Arimondo, PB, Glaser, P, Aigle, B, Bode, HB, Moreira, R, Li, Y, Luzhetskyy, A, Medema, MH, Pernodet, JL, Stadler, M, Tormo, JR, Genilloud, O, Truman, AW, Weissman, KJ, Takano, E, Sabatini, S, Stegmann, E, Brötz-Oesterhelt, H, Wohlleben, W, Seemann, M, Empting, M, Hirsch, AKH, Loretz, B, Lehr, CM, Titz, A, Herrmann, J, Jaeger, T, Alt, S, Hesterkamp, T, Winterhalter, M, Schiefer, A, Pfarr, K, Hoerauf, A, Graz, H, Graz, M, Lindvall, M, Ramurthy, S, Karlén, A, van Dongen, M, Petkovic, H, Keller, A, Peyrane, F, Donadio, S, Fraisse, L, Piddock, LJV, Gilbert, IH, Moser, HE & Müller, R 2021, 'Towards the sustainable discovery and development of new antibiotics', Nature Reviews Chemistry, vol. 5, pp. 726-749. https://doi.org/10.1038/s41570-021-00313-1

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AU - Miethke, Marcus

AU - Pieroni, Marco

AU - Weber, Tilmann

AU - Brönstrup, Mark

AU - Hammann, Peter

AU - Halby, Ludovic

AU - Arimondo, Paola B.

AU - Glaser, Philippe

AU - Aigle, Bertrand

AU - Bode, Helge B.

AU - Moreira, Rui

AU - Li, Yanyan

AU - Luzhetskyy, Andriy

AU - Medema, Marnix H.

AU - Pernodet, Jean Luc

AU - Stadler, Marc

AU - Tormo, José Rubén

AU - Genilloud, Olga

AU - Truman, Andrew W.

AU - Weissman, Kira J.

AU - Takano, Eriko

AU - Sabatini, Stefano

AU - Stegmann, Evi

AU - Brötz-Oesterhelt, Heike

AU - Wohlleben, Wolfgang

AU - Seemann, Myriam

AU - Empting, Martin

AU - Hirsch, Anna K.H.

AU - Loretz, Brigitta

AU - Lehr, Claus Michael

AU - Titz, Alexander

AU - Herrmann, Jennifer

AU - Jaeger, Timo

AU - Alt, Silke

AU - Hesterkamp, Thomas

AU - Winterhalter, Mathias

AU - Schiefer, Andrea

AU - Pfarr, Kenneth

AU - Hoerauf, Achim

AU - Graz, Heather

AU - Graz, Michael

AU - Lindvall, Mika

AU - Ramurthy, Savithri

AU - Karlén, Anders

AU - van Dongen, Maarten

AU - Petkovic, Hrvoje

AU - Keller, Andreas

AU - Peyrane, Frédéric

AU - Donadio, Stefano

AU - Fraisse, Laurent

AU - Piddock, Laura J.V.

AU - Gilbert, Ian H.

AU - Moser, Heinz E.

AU - Müller, Rolf

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PY - 2021

Y1 - 2021

N2 - An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.

AB - An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations.

U2 - 10.1038/s41570-021-00313-1

DO - 10.1038/s41570-021-00313-1

M3 - Review

C2 - 34426795

AN - SCOPUS:85110714419

SN - 2397-3358

VL - 5

SP - 726

EP - 749

JO - Nature Reviews Chemistry

JF - Nature Reviews Chemistry

ER -

Towards the sustainable discovery and development of new antibiotics

Abstract

Bibliographical note

UN SDGs

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