Open Access
Nature, volume 545, issue 7654, pages 299-304
Predictive compound accumulation rules yield a broad-spectrum antibiotic
Richter Michelle F
1
,
Drown Bryon S
1
,
Riley Andrew P
1
,
García Alfredo
1
,
Shirai Tomohiro
1
,
Svec Riley L
1
,
Hergenrother Paul J.
1
1
Department of Chemistry and Institute for Genomic Biology, University of Illinois, Urbana, USA
|
Publication type: Journal Article
Publication date: 2017-05-10
PubMed ID:
28489819
Multidisciplinary
Abstract
Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based on retrospective analyses of antibacterial agents, which suggest that polarity and molecular weight are key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate that these findings will aid in the discovery and development of antibiotics against Gram-negative bacteria.
Citations by journals
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Citations by publishers
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American Chemical Society (ACS)
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170 publications, 27.38%
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Elsevier
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Wiley
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7 publications, 1.13%
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Bentham Science
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5 publications, 0.81%
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King Saud University
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1 publication, 0.16%
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American Society for Biochemistry and Molecular Biology
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American Society for Biochemistry and Molecular Biology
1 publication, 0.16%
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KeAi Communications Co.
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Korean Society of Industrial Engineering Chemistry, 1, 0.16%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Richter M. F. et al. Predictive compound accumulation rules yield a broad-spectrum antibiotic // Nature. 2017. Vol. 545. No. 7654. pp. 299-304.
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Richter M. F., Drown B. S., Riley A. P., García A., Shirai T., Svec R. L., Hergenrother P. J. Predictive compound accumulation rules yield a broad-spectrum antibiotic // Nature. 2017. Vol. 545. No. 7654. pp. 299-304.
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TY - JOUR
DO - 10.1038/nature22308
UR - https://doi.org/10.1038%2Fnature22308
TI - Predictive compound accumulation rules yield a broad-spectrum antibiotic
T2 - Nature
AU - Richter, Michelle F
AU - Drown, Bryon S
AU - Riley, Andrew P
AU - García, Alfredo
AU - Shirai, Tomohiro
AU - Svec, Riley L
AU - Hergenrother, Paul J.
PY - 2017
DA - 2017/05/10 00:00:00
PB - Springer Nature
SP - 299-304
IS - 7654
VL - 545
PMID - 28489819
SN - 0028-0836
SN - 1476-4687
ER -
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@article{2017_Richter,
author = {Michelle F Richter and Bryon S Drown and Andrew P Riley and Alfredo García and Tomohiro Shirai and Riley L Svec and Paul J. Hergenrother},
title = {Predictive compound accumulation rules yield a broad-spectrum antibiotic},
journal = {Nature},
year = {2017},
volume = {545},
publisher = {Springer Nature},
month = {may},
url = {https://doi.org/10.1038%2Fnature22308},
number = {7654},
pages = {299--304},
doi = {10.1038/nature22308}
}
Cite this
MLA
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Richter, Michelle F., et al. “Predictive compound accumulation rules yield a broad-spectrum antibiotic.” Nature, vol. 545, no. 7654, May. 2017, pp. 299-304. https://doi.org/10.1038%2Fnature22308.