Title |
A new antibiotic with potent activity targets MscL
|
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Published in |
The Journal of Antibiotics, February 2015
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DOI | 10.1038/ja.2015.4 |
Pubmed ID | |
Authors |
Irene Iscla, Robin Wray, Paul Blount, Jonah Larkins-Ford, Annie L Conery, Frederick M Ausubel, Soumya Ramu, Angela Kavanagh, Johnny X Huang, Mark A Blaskovich, Matthew A Cooper, Andres Obregon-Henao, Ian Orme, Edwin S Tjandra, Uwe H Stroeher, Melissa H Brown, Cindy Macardle, Nick van Holst, Chee Ling Tong, Ashley D Slattery, Christopher T Gibson, Colin L Raston, Ramiz A Boulos |
Abstract |
The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections.The Journal of Antibiotics advance online publication, 4 February 2015; doi:10.1038/ja.2015.4. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Australia | 3 | 21% |
United Kingdom | 2 | 14% |
United States | 1 | 7% |
Germany | 1 | 7% |
Canada | 1 | 7% |
Unknown | 6 | 43% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 10 | 71% |
Practitioners (doctors, other healthcare professionals) | 2 | 14% |
Scientists | 1 | 7% |
Science communicators (journalists, bloggers, editors) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 2% |
Australia | 2 | 2% |
Indonesia | 1 | 1% |
United Kingdom | 1 | 1% |
Poland | 1 | 1% |
Unknown | 74 | 91% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 16 | 20% |
Researcher | 13 | 16% |
Student > Master | 10 | 12% |
Student > Bachelor | 9 | 11% |
Student > Postgraduate | 6 | 7% |
Other | 13 | 16% |
Unknown | 14 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 20 | 25% |
Biochemistry, Genetics and Molecular Biology | 13 | 16% |
Chemistry | 9 | 11% |
Medicine and Dentistry | 5 | 6% |
Immunology and Microbiology | 4 | 5% |
Other | 15 | 19% |
Unknown | 15 | 19% |