Open Access
Nature Communications, volume 11, issue 1, publication number 1455
Ca2+-Daptomycin targets cell wall biosynthesis by forming a tripartite complex with undecaprenyl-coupled intermediates and membrane lipids
Grein Fabian
1, 2
,
Müller Anna
1
,
Scherer Katharina M.
3
,
Liu Xinliang
3
,
Ludwig Kevin C
1
,
Klöckner Anna
1, 2
,
Strach Manuel
1
,
SAHL HANS-GEORG
4
,
Kubitscheck Ulrich
3
,
Schneider Tanja
1, 2
1
Institute for Pharmaceutical Microbiology, University Hospital Bonn, University of Bonn, Bonn, Germany
|
2
German Center for Infection Research (DZIF), partner site Bonn-Cologne, Bonn, Germany
|
3
Institute for Physical and Theoretical Chemistry, University of Bonn, Bonn, Germany
|
4
Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, University of Bonn, Bonn, Germany
|
Publication type: Journal Article
Publication date: 2020-03-19
Journal:
Nature Communications
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 16.6
ISSN: 20411723
PubMed ID:
32193379
General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy
Abstract
The lipopeptide daptomycin is used as an antibiotic to treat severe infections with gram-positive pathogens, such as methicillin resistant Staphylococcus aureus (MRSA) and drug-resistant enterococci. Its precise mechanism of action is incompletely understood, and a specific molecular target has not been identified. Here we show that Ca2+-daptomycin specifically interacts with undecaprenyl-coupled cell envelope precursors in the presence of the anionic phospholipid phosphatidylglycerol, forming a tripartite complex. We use microbiological and biochemical assays, in combination with fluorescence and optical sectioning microscopy of intact staphylococcal cells and model membrane systems. Binding primarily occurs at the staphylococcal septum and interrupts cell wall biosynthesis. This is followed by delocalisation of components of the peptidoglycan biosynthesis machinery and massive membrane rearrangements, which may account for the pleiotropic cellular events previously reported. The identification of carrier-bound cell wall precursors as specific targets explains the specificity of daptomycin for bacterial cells. Our work reconciles apparently inconsistent previous results, and supports a concise model for the mode of action of daptomycin. The mechanism of action of daptomycin, a lipopeptidic antibiotic, is unclear. Here, the authors show that Ca2+-daptomycin simultaneously interacts with lipid-coupled precursors of the bacterial cell envelope and with the anionic phospholipid phosphatidylglycerol, forming a tripartite complex.
Citations by journals
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3 publications, 2.36%
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2 publications, 1.57%
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2 publications, 1.57%
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2 publications, 1.57%
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2 publications, 1.57%
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2 publications, 1.57%
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1 publication, 0.79%
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1 publication, 0.79%
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1 publication, 0.79%
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Frontiers in Cellular and Infection Microbiology
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1 publication, 0.79%
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Frontiers in Molecular Biosciences
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Frontiers in Molecular Biosciences
1 publication, 0.79%
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Journal of Membrane Biology
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Journal of Membrane Biology
1 publication, 0.79%
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Citations by publishers
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2
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18
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Multidisciplinary Digital Publishing Institute (MDPI)
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18 publications, 14.17%
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American Chemical Society (ACS)
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15 publications, 11.81%
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American Society for Microbiology
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American Society for Microbiology
14 publications, 11.02%
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Elsevier
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Elsevier
12 publications, 9.45%
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Wiley
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Wiley
11 publications, 8.66%
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Springer Nature
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Springer Nature
11 publications, 8.66%
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Frontiers Media S.A.
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Frontiers Media S.A.
7 publications, 5.51%
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Royal Society of Chemistry (RSC)
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6 publications, 4.72%
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Microbiology Society
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3 publications, 2.36%
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American Society for Biochemistry and Molecular Biology
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American Society for Biochemistry and Molecular Biology
2 publications, 1.57%
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Taylor & Francis
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Taylor & Francis
2 publications, 1.57%
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Future Medicine
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Future Medicine
1 publication, 0.79%
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American Association for the Advancement of Science (AAAS)
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American Association for the Advancement of Science (AAAS)
1 publication, 0.79%
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Shenyang Pharmaceutical University
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Shenyang Pharmaceutical University, 1, 0.79%
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1 publication, 0.79%
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Public Library of Science (PLoS)
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1 publication, 0.79%
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Social Science Electronic Publishing
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Social Science Electronic Publishing
1 publication, 0.79%
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eLife Sciences Publications
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eLife Sciences Publications
1 publication, 0.79%
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Oxford University Press
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Oxford University Press
1 publication, 0.79%
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Proceedings of the National Academy of Sciences (PNAS)
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Proceedings of the National Academy of Sciences (PNAS)
1 publication, 0.79%
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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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Grein F. et al. Ca2+-Daptomycin targets cell wall biosynthesis by forming a tripartite complex with undecaprenyl-coupled intermediates and membrane lipids // Nature Communications. 2020. Vol. 11. No. 1. 1455
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Grein F., Müller A., Scherer K. M., Liu X., Ludwig K. C., Klöckner A., Strach M., SAHL H., Kubitscheck U., Schneider T. Ca2+-Daptomycin targets cell wall biosynthesis by forming a tripartite complex with undecaprenyl-coupled intermediates and membrane lipids // Nature Communications. 2020. Vol. 11. No. 1. 1455
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TY - JOUR
DO - 10.1038/s41467-020-15257-1
UR - https://doi.org/10.1038%2Fs41467-020-15257-1
TI - Ca2+-Daptomycin targets cell wall biosynthesis by forming a tripartite complex with undecaprenyl-coupled intermediates and membrane lipids
T2 - Nature Communications
AU - Grein, Fabian
AU - Müller, Anna
AU - Scherer, Katharina M.
AU - Liu, Xinliang
AU - Ludwig, Kevin C
AU - Klöckner, Anna
AU - Strach, Manuel
AU - SAHL, HANS-GEORG
AU - Kubitscheck, Ulrich
AU - Schneider, Tanja
PY - 2020
DA - 2020/03/19 00:00:00
PB - Springer Nature
IS - 1
VL - 11
PMID - 32193379
SN - 2041-1723
ER -
Cite this
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@article{2020_Grein,
author = {Fabian Grein and Anna Müller and Katharina M. Scherer and Xinliang Liu and Kevin C Ludwig and Anna Klöckner and Manuel Strach and HANS-GEORG SAHL and Ulrich Kubitscheck and Tanja Schneider},
title = {Ca2+-Daptomycin targets cell wall biosynthesis by forming a tripartite complex with undecaprenyl-coupled intermediates and membrane lipids},
journal = {Nature Communications},
year = {2020},
volume = {11},
publisher = {Springer Nature},
month = {mar},
url = {https://doi.org/10.1038%2Fs41467-020-15257-1},
number = {1},
doi = {10.1038/s41467-020-15257-1}
}