Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria
Abstract Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated wi...
Guardado en:
Autores principales: | , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2017
|
Materias: | |
Acceso en línea: | https://doaj.org/article/36da0b6203544be3912a0cf3797ab0ad |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:36da0b6203544be3912a0cf3797ab0ad |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:36da0b6203544be3912a0cf3797ab0ad2021-12-02T12:30:35ZZn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria10.1038/s41598-017-04868-22045-2322https://doaj.org/article/36da0b6203544be3912a0cf3797ab0ad2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04868-2https://doaj.org/toc/2045-2322Abstract Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and we show that the activity of other glycopeptide antibiotics with this feature can also be similarly augmented by Zn(II). Construction and analysis of a model strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis during normal growth supports the hypothesis that Zn(II) mediated vancomycin polymerization enhances the binding affinity towards these precursors.Ashraf ZarkanHeather-Rose MacklyneDimitri Y. ChirgadzeAndrew D. BondAndrew R. HeskethHee-Jeon HongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Ashraf Zarkan Heather-Rose Macklyne Dimitri Y. Chirgadze Andrew D. Bond Andrew R. Hesketh Hee-Jeon Hong Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria |
description |
Abstract Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and we show that the activity of other glycopeptide antibiotics with this feature can also be similarly augmented by Zn(II). Construction and analysis of a model strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis during normal growth supports the hypothesis that Zn(II) mediated vancomycin polymerization enhances the binding affinity towards these precursors. |
format |
article |
author |
Ashraf Zarkan Heather-Rose Macklyne Dimitri Y. Chirgadze Andrew D. Bond Andrew R. Hesketh Hee-Jeon Hong |
author_facet |
Ashraf Zarkan Heather-Rose Macklyne Dimitri Y. Chirgadze Andrew D. Bond Andrew R. Hesketh Hee-Jeon Hong |
author_sort |
Ashraf Zarkan |
title |
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria |
title_short |
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria |
title_full |
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria |
title_fullStr |
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria |
title_full_unstemmed |
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria |
title_sort |
zn(ii) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/36da0b6203544be3912a0cf3797ab0ad |
work_keys_str_mv |
AT ashrafzarkan zniimediatesvancomycinpolymerizationandpotentiatesitsantibioticactivityagainstresistantbacteria AT heatherrosemacklyne zniimediatesvancomycinpolymerizationandpotentiatesitsantibioticactivityagainstresistantbacteria AT dimitriychirgadze zniimediatesvancomycinpolymerizationandpotentiatesitsantibioticactivityagainstresistantbacteria AT andrewdbond zniimediatesvancomycinpolymerizationandpotentiatesitsantibioticactivityagainstresistantbacteria AT andrewrhesketh zniimediatesvancomycinpolymerizationandpotentiatesitsantibioticactivityagainstresistantbacteria AT heejeonhong zniimediatesvancomycinpolymerizationandpotentiatesitsantibioticactivityagainstresistantbacteria |
_version_ |
1718394326825828352 |