Open Access

Scientific Reports, volume 9, issue 1, publication number 11460

Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant

Halfon Yehuda ¹

Matzov Donna ¹

Eyal Zohar ¹

Bashan A. ¹

Zimmerman Ella ¹

Kjeldgaard Jette ²

Ingmer Hanne ³

Yonath Ada ¹

Hide authors affiliations Show authors affiliations: 3 affiliations

The Weizmann Institute of Science, The Department of structural biology, Rehovot, Israel |

National Food Institute, Technical University of Denmark, Kemitorvet, DK-2800, Kgs, Lyngby, Denmark |

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark |

Publication type: Journal Article

Publication date: 2019-08-07

Springer Nature

Journal: Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor: 4.6

ISSN: 20452322

DOI: 10.1038/s41598-019-48019-1

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PubMed ID: 31391518

Multidisciplinary

Abstract

The clinical use of the antibiotic erythromycin (ery) is hampered owing to the spread of resistance genes that are mostly mutating rRNA around the ery binding site at the entrance to the protein exit tunnel. Additional effective resistance mechanisms include deletion or insertion mutations in ribosomal protein uL22, which lead to alterations of the exit tunnel shape, located 16 Å away from the drug’s binding site. We determined the cryo-EM structures of the Staphylococcus aureus 70S ribosome, and its ery bound complex with a two amino acid deletion mutation in its ß hairpin loop, which grants the bacteria resistance to ery. The structures reveal that, although the binding of ery is stable, the movement of the flexible shorter uL22 loop towards the tunnel wall creates a wider path for nascent proteins, thus enabling bypass of the barrier formed by the drug. Moreover, upon drug binding, the tunnel widens further.

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Citations by journals

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Molecules	Molecules, 1, 3.03% Molecules 1 publication, 3.03%
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 1, 3.03% International Journal of Molecular Sciences 1 publication, 3.03%
Biomolecules	Biomolecules, 1, 3.03% Biomolecules 1 publication, 3.03%
Genes	Genes, 1, 3.03% Genes 1 publication, 3.03%
Frontiers in Microbiology	Frontiers in Microbiology, 1, 3.03% Frontiers in Microbiology 1 publication, 3.03%
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PeerJ	PeerJ, 1, 3.03% PeerJ 1 publication, 3.03%
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Emerging Microbes and Infections	Emerging Microbes and Infections, 1, 3.03% Emerging Microbes and Infections 1 publication, 3.03%
FEMS Microbiology Reviews	FEMS Microbiology Reviews, 1, 3.03% FEMS Microbiology Reviews 1 publication, 3.03%
Proceedings of the National Academy of Sciences of the United States of America	Proceedings of the National Academy of Sciences of the United States of America, 1, 3.03% Proceedings of the National Academy of Sciences of the United States of America 1 publication, 3.03%
eLife	eLife, 1, 3.03% eLife 1 publication, 3.03%
Total Environment Research Themes	Total Environment Research Themes, 1, 3.03% Total Environment Research Themes 1 publication, 3.03%
Acta Crystallographica Section D: Structural Biology	Acta Crystallographica Section D: Structural Biology, 1, 3.03% Acta Crystallographica Section D: Structural Biology 1 publication, 3.03%
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Citations by publishers

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Springer Nature	Springer Nature, 5, 15.15% Springer Nature 5 publications, 15.15%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 4, 12.12% Multidisciplinary Digital Publishing Institute (MDPI) 4 publications, 12.12%
Elsevier	Elsevier, 3, 9.09% Elsevier 3 publications, 9.09%
American Society for Microbiology	American Society for Microbiology, 3, 9.09% American Society for Microbiology 3 publications, 9.09%
Oxford University Press	Oxford University Press, 3, 9.09% Oxford University Press 3 publications, 9.09%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 2, 6.06% Cold Spring Harbor Laboratory 2 publications, 6.06%
Wiley	Wiley, 2, 6.06% Wiley 2 publications, 6.06%
Frontiers Media S.A.	Frontiers Media S.A., 1, 3.03% Frontiers Media S.A. 1 publication, 3.03%
PeerJ	PeerJ, 1, 3.03% PeerJ 1 publication, 3.03%
International Association for Food Protection	International Association for Food Protection, 1, 3.03% International Association for Food Protection 1 publication, 3.03%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 1, 3.03% Proceedings of the National Academy of Sciences (PNAS) 1 publication, 3.03%
eLife Sciences Publications	eLife Sciences Publications, 1, 3.03% eLife Sciences Publications 1 publication, 3.03%
International Union of Crystallography (IUCr)	International Union of Crystallography (IUCr), 1, 3.03% International Union of Crystallography (IUCr) 1 publication, 3.03%
	1 2 3 4 5

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Halfon Y. et al. Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant // Scientific Reports. 2019. Vol. 9. No. 1. 11460

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Halfon Y., Matzov D., Eyal Z., Bashan A., Zimmerman E., Kjeldgaard J., Ingmer H., Yonath A. Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant // Scientific Reports. 2019. Vol. 9. No. 1. 11460

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TY - JOUR

DO - 10.1038/s41598-019-48019-1

UR - https://doi.org/10.1038%2Fs41598-019-48019-1

TI - Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant

T2 - Scientific Reports

AU - Halfon, Yehuda

AU - Matzov, Donna

AU - Eyal, Zohar

AU - Bashan, A.

AU - Zimmerman, Ella

AU - Kjeldgaard, Jette

AU - Ingmer, Hanne

AU - Yonath, Ada

PY - 2019

DA - 2019/08/07 00:00:00

PB - Springer Nature

IS - 1

VL - 9

PMID - 31391518

SN - 2045-2322

ER -

BibTex

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BibTex Copy

@article{2019_Halfon,

author = {Yehuda Halfon and Donna Matzov and Zohar Eyal and A. Bashan and Ella Zimmerman and Jette Kjeldgaard and Hanne Ingmer and Ada Yonath},

title = {Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant},

journal = {Scientific Reports},

year = {2019},

volume = {9},

publisher = {Springer Nature},

month = {aug},

url = {https://doi.org/10.1038%2Fs41598-019-48019-1},

number = {1},

doi = {10.1038/s41598-019-48019-1}

}

Found error?

Publisher

Springer Nature

Journal

Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor

4.6

ISSN

20452322 (Print)