Open Access
Nature Communications, volume 6, issue 1, publication number 6947
Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria
Parkinson Elizabeth I
1
,
Bair Joseph S
1
,
Nakamura Bradley A
1
,
Lee Hyang Y
1
,
Kuttab Hani I.
1
,
Southgate Emma H
1
,
Lezmi Stéphane
2
,
Lau Gee W.
2
,
Hergenrother Paul J.
1
1
Department of Chemistry, Roger Adams Laboratory, University of Illinois at Urbana-Champaign, Urbana, USA
|
2
College of Veterinary Medicine, Veterinary Medicine Basic Sciences Building, University of Illinois at Urbana-Champaign, Urbana, USA
|
Publication type: Journal Article
Publication date: 2015-04-24
Journal:
Nature Communications
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 16.6
ISSN: 20411723
PubMed ID:
25907309
General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
Abstract
Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections. Fluoroquinolone antibiotics are widely used to treat serious bacterial infections, but resistance is an increasing problem. Here the authors describe the synthesis and characterization of novel deoxynybomycin derivatives that exhibit activity against fluoroquinolone-resistant infections in an in vivomodel.
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- We do not take into account publications that without a DOI.
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- Statistics recalculated weekly.
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Parkinson E. I. et al. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria // Nature Communications. 2015. Vol. 6. No. 1. 6947
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Parkinson E. I., Bair J. S., Nakamura B. A., Lee H. Y., Kuttab H. I., Southgate E. H., Lezmi S., Lau G. W., Hergenrother P. J. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria // Nature Communications. 2015. Vol. 6. No. 1. 6947
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TY - JOUR
DO - 10.1038/ncomms7947
UR - https://doi.org/10.1038%2Fncomms7947
TI - Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria
T2 - Nature Communications
AU - Parkinson, Elizabeth I
AU - Bair, Joseph S
AU - Nakamura, Bradley A
AU - Lee, Hyang Y
AU - Kuttab, Hani I.
AU - Southgate, Emma H
AU - Lezmi, Stéphane
AU - Lau, Gee W.
AU - Hergenrother, Paul J.
PY - 2015
DA - 2015/04/24 00:00:00
PB - Springer Nature
IS - 1
VL - 6
PMID - 25907309
SN - 2041-1723
ER -
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@article{2015_Parkinson,
author = {Elizabeth I Parkinson and Joseph S Bair and Bradley A Nakamura and Hyang Y Lee and Hani I. Kuttab and Emma H Southgate and Stéphane Lezmi and Gee W. Lau and Paul J. Hergenrother},
title = {Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria},
journal = {Nature Communications},
year = {2015},
volume = {6},
publisher = {Springer Nature},
month = {apr},
url = {https://doi.org/10.1038%2Fncomms7947},
number = {1},
doi = {10.1038/ncomms7947}
}