Journal ArticleDOI
Thinking Outside the Box-Novel Antibacterials To Tackle the Resistance Crisis.
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TLDR
This Review encompasses several aspects of the antibiotic development pipeline from very early strategies to mature drugs, and aims to connect innovative antimicrobial approaches to stimulate interdisciplinary partnerships between chemists from academia and industry.Abstract:
The public view on antibiotics as reliable medicines changed when reports about "resistant superbugs" appeared in the news. While reasons for this resistance development are easily spotted, solutions for re-establishing effective antibiotics are still in their infancy. This Review encompasses several aspects of the antibiotic development pipeline from very early strategies to mature drugs. An interdisciplinary overview is given of methods suitable for mining novel antibiotics and strategies discussed to unravel their modes of action. Select examples of antibiotics recently identified by using these platforms not only illustrate the efficiency of these measures, but also highlight promising clinical candidates with therapeutic potential. Furthermore, the concept of molecules that disarm pathogens by addressing gatekeepers of virulence will be covered. The Review concludes with an evaluation of antibacterials currently in clinical development. Overall, this Review aims to connect select innovative antimicrobial approaches to stimulate interdisciplinary partnerships between chemists from academia and industry.read more
Citations
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Journal ArticleDOI
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,Helge B. Bode,Rui Moreira,Yanyan Li,Andriy Luzhetskyy,Marnix H. Medema,Jean-Luc Pernodet,Marc Stadler,José R. 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 Petković,Andreas Keller,Frédéric Peyrane,Stefano Donadio,Laurent Fraisse,Laura J. V. Piddock,Ian H. Gilbert,Heinz E. Moser,Rolf Müller +54 more
TL;DR: In this paper, the authors present a strategic blueprint to substantially improve our ability to discover and develop new antibiotics, and propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding.
Journal ArticleDOI
Defect‐Rich Adhesive Nanozymes as Efficient Antibiotics for Enhanced Bacterial Inhibition
Fangfang Cao,Fangfang Cao,Lu Zhang,Huanhuan Wang,Huanhuan Wang,Yawen You,Yawen You,Ying Wang,Nan Gao,Jinsong Ren,Xiaogang Qu +10 more
TL;DR: For the first time, a one-step strategy to simultaneously promote the binding capacity and catalytic activity of nanozymes by constructing rough surfaces with exposed defect-rich active edges is reported, paving a new way for the development of alternative antibiotcs.
Journal ArticleDOI
Construction of Nanozyme-Hydrogel for Enhanced Capture and Elimination of Bacteria
Yanjuan Sang,Yanjuan Sang,Wei Li,Hao Liu,Hao Liu,Lu Zhang,Huan Wang,Huan Wang,Zhengwei Liu,Jinsong Ren,Xiaogang Qu +10 more
Journal ArticleDOI
Antibiotics in the clinical pipeline in October 2019
Mark S. Butler,David L. Paterson +1 more
TL;DR: There is still a significant gap in the pipeline for the development of new antibacterials with activity against β-metallolactamases, orally administered with broad spectrum G−ve activity, and new treatments for MDR Acinetobacter and gonorrhea.
Journal ArticleDOI
Antibiotics Separation with MXene Membranes Based on Regularly Stacked High‐Aspect‐Ratio Nanosheets
Zhong-Kun Li,Yanying Wei,Xue Gao,Li Ding,Zong Lu,Junjie Deng,Xianfeng Yang,Jürgen Caro,Haihui Wang +8 more
TL;DR: Seven kinds of typical antibiotics are successfully separated from the corresponding aqueous and ethanolic solutions using highly regular laminated membranes made with 2-4 μm titanium carbide nanosheets.
References
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A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes.
Journal ArticleDOI
Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides.
TL;DR: A novel regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes to azides on solid-phase is reported, and the X-ray structure of 2-azido-2-methylpropanoic acid has been solved, to yield structural information on the 1, 3-dipoles entering the reaction.
Journal ArticleDOI
Drugs for bad bugs: confronting the challenges of antibacterial discovery
TL;DR: The experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years is shared, and what is learned is looked at and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
Journal ArticleDOI
A new antibiotic kills pathogens without detectable resistance
Losee Lucy Ling,Tanja Schneider,Aaron J. Peoples,Amy Spoering,Ina Engels,Brian P. Conlon,A. Mueller,Till F. Schäberle,Dallas Hughes,Slava S. Epstein,M. Jones,Linos Lazarides,Victoria Alexandra Steadman,Cohen Dr,Cintia R. Felix,Fetterman Ka,William Millett,Anthony Nitti,Ashley Zullo,Chao Chen,Kim Lewis +20 more
TL;DR: The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance, as well as several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors.
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The structure of beta-lactamases.
TL;DR: In this article, it was shown that the β-lactamases have a polyphyletic origin and all the enzymes of currently known amino acid sequence belong to one homology group, called class A enzymes.
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