Title |
Optimized arylomycins are a new class of Gram-negative antibiotics
|
---|---|
Published in |
Nature, September 2018
|
DOI | 10.1038/s41586-018-0483-6 |
Pubmed ID | |
Authors |
Peter A. Smith, Michael F. T. Koehler, Hany S. Girgis, Donghong Yan, Yongsheng Chen, Yuan Chen, James J. Crawford, Matthew R. Durk, Robert I. Higuchi, Jing Kang, Jeremy Murray, Prasuna Paraselli, Summer Park, Wilson Phung, John G. Quinn, Tucker C. Roberts, Lionel Rougé, Jacob B. Schwarz, Elizabeth Skippington, John Wai, Min Xu, Zhiyong Yu, Hua Zhang, Man-Wah Tan, Christopher E. Heise |
Abstract |
Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts no new class of antibiotic with activity against Gram-negative bacteria has been approved in over fifty years. Natural products and their derivatives have a key role in combating Gram-negative pathogens. Here we report chemical optimization of the arylomycins-a class of natural products with weak activity and limited spectrum-to obtain G0775, a molecule with potent, broad-spectrum activity against Gram-negative bacteria. G0775 inhibits the essential bacterial type I signal peptidase, a new antibiotic target, through an unprecedented molecular mechanism. It circumvents existing antibiotic resistance mechanisms and retains activity against contemporary multidrug-resistant Gram-negative clinical isolates in vitro and in several in vivo infection models. These findings demonstrate that optimized arylomycin analogues such as G0775 could translate into new therapies to address the growing threat of multidrug-resistant Gram-negative infections. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 85 | 19% |
United Kingdom | 51 | 11% |
France | 29 | 7% |
Canada | 16 | 4% |
Australia | 13 | 3% |
Spain | 10 | 2% |
Germany | 9 | 2% |
Saudi Arabia | 8 | 2% |
Mexico | 7 | 2% |
Other | 68 | 15% |
Unknown | 148 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 259 | 58% |
Scientists | 162 | 36% |
Practitioners (doctors, other healthcare professionals) | 15 | 3% |
Science communicators (journalists, bloggers, editors) | 8 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 570 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 150 | 26% |
Researcher | 85 | 15% |
Student > Bachelor | 66 | 12% |
Student > Master | 39 | 7% |
Student > Doctoral Student | 31 | 5% |
Other | 73 | 13% |
Unknown | 126 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 123 | 22% |
Biochemistry, Genetics and Molecular Biology | 119 | 21% |
Agricultural and Biological Sciences | 60 | 11% |
Immunology and Microbiology | 39 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 28 | 5% |
Other | 55 | 10% |
Unknown | 146 | 26% |