A new antibiotic with potent activity targets MscL

Iscla, Irene, Wray, Robin, Blount, Paul, Larkins-Ford, Johah, Conery, Annie L., Ausubel, Frederick M., Ramu, Soumya, Kavanagh, Angela, Huang, Johnny X., Blaskovich, Mark A., Cooper, Matthew A., Obregon-Henao, Andres, Orme, Ian, Tjandra, Edwin S., Stroeher, Uwe H., Brown, Melissa H., Macardle, Cindy, van Holst, Nick, Tong, Chee Ling, Slattery, Ashley D., Gibson, Christopher T., Raston, Colin L. and Boulos, Ramiz A. (2015) A new antibiotic with potent activity targets MscL. The Journal of Antibiotics, 68 7: 453-462. doi:10.1038/ja.2015.4

Author Iscla, Irene
Wray, Robin
Blount, Paul
Larkins-Ford, Johah
Conery, Annie L.
Ausubel, Frederick M.
Ramu, Soumya
Kavanagh, Angela
Huang, Johnny X.
Blaskovich, Mark A.
Cooper, Matthew A.
Obregon-Henao, Andres
Orme, Ian
Tjandra, Edwin S.
Stroeher, Uwe H.
Brown, Melissa H.
Macardle, Cindy
van Holst, Nick
Tong, Chee Ling
Slattery, Ashley D.
Gibson, Christopher T.
Raston, Colin L.
Boulos, Ramiz A.
Title A new antibiotic with potent activity targets MscL
Journal name The Journal of Antibiotics   Check publisher's open access policy
ISSN 0021-8820
Publication date 2015-07-01
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ja.2015.4
Open Access Status DOI
Volume 68
Issue 7
Start page 453
End page 462
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Tue, 14 Apr 2015, 20:09:43 EST by Susan Allen on behalf of Institute for Molecular Bioscience