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

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Standard

Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant. / Halfon, Yehuda; Matzov, Donna; Eyal, Zohar; Bashan, Anat; Zimmerman, Ella; Kjeldgaard, Jette; Ingmer, Hanne; Yonath, Ada.

I: Scientific Reports, Bind 9, Nr. 1, 11460, 2019.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Halfon, Y, Matzov, D, Eyal, Z, Bashan, A, Zimmerman, E, Kjeldgaard, J, Ingmer, H & Yonath, A 2019, 'Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant', Scientific Reports, bind 9, nr. 1, 11460. https://doi.org/10.1038/s41598-019-48019-1

APA

Halfon, Y., Matzov, D., Eyal, Z., Bashan, A., Zimmerman, E., Kjeldgaard, J., Ingmer, H., & Yonath, A. (2019). Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant. Scientific Reports, 9(1), [11460]. https://doi.org/10.1038/s41598-019-48019-1

Vancouver

Halfon Y, Matzov D, Eyal Z, Bashan A, Zimmerman E, Kjeldgaard J o.a. Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant. Scientific Reports. 2019;9(1). 11460. https://doi.org/10.1038/s41598-019-48019-1

Author

Halfon, Yehuda ; Matzov, Donna ; Eyal, Zohar ; Bashan, Anat ; Zimmerman, Ella ; Kjeldgaard, Jette ; Ingmer, Hanne ; Yonath, Ada. / Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant. I: Scientific Reports. 2019 ; Bind 9, Nr. 1.

Bibtex

@article{efabbaeccccb43188e3e116e449a61dd,
title = "Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant",
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 {\AA} away from the drug{\textquoteright}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.",
author = "Yehuda Halfon and Donna Matzov and Zohar Eyal and Anat Bashan and Ella Zimmerman and Jette Kjeldgaard and Hanne Ingmer and Ada Yonath",
year = "2019",
doi = "10.1038/s41598-019-48019-1",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant

AU - Halfon, Yehuda

AU - Matzov, Donna

AU - Eyal, Zohar

AU - Bashan, Anat

AU - Zimmerman, Ella

AU - Kjeldgaard, Jette

AU - Ingmer, Hanne

AU - Yonath, Ada

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-019-48019-1

DO - 10.1038/s41598-019-48019-1

M3 - Journal article

C2 - 31391518

AN - SCOPUS:85070353991

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 11460

ER -

ID: 226376411