umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Evaluation of the characteristics of leucyl-tRNA synthetase (LeuRS) inhibitor AN3365 in combination with different antibiotic classes
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
Show others and affiliations
2016 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 11, 1857-1864 p.Article in journal (Refereed) Published
Abstract [en]

Aminoacyl tRNA synthetases are enzymes involved in the key process of coupling an amino acid to its cognate tRNA. AN3365 is a novel antibiotic that specifically targets leucyl-tRNA synthetase, whose development was halted after evaluation in phase II clinical trials owing to the rapid selection of resistance. In an attempt to bring AN3365 back into the developmental pipeline we have evaluated the efficacy of AN3365 in combination with different classes of antibiotic and characterized its mechanism of action. Although we detect no synergy or antagonism in combination with a range of antibiotic classes, a combination of AN3365 with colistin reduces the accumulation of AN3365-resistant and colistin resistance mutations. We also demonstrate that treatment with AN3365 results in the dramatic accumulation of the alarmone (p)ppGpp, the effector of the stringent response-a key player in antibiotic tolerance.

Place, publisher, year, edition, pages
2016. Vol. 35, no 11, 1857-1864 p.
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-129885DOI: 10.1007/s10096-016-2738-1ISI: 000386157300018PubMedID: 27506217OAI: oai:DiVA.org:umu-129885DiVA: diva2:1065476
Available from: 2017-01-16 Created: 2017-01-10 Last updated: 2017-01-16Bibliographically approved

Open Access in DiVA

fulltext(737 kB)22 downloads
File information
File name FULLTEXT01.pdfFile size 737 kBChecksum SHA-512
c97b84ce51e6fa5a6f09ed32d3df5ab9a8c56cc66d50886e08dfc2271d91d92f1b6c98ae4d0b87949d9e965ed05145adf62a77ac737641119163da438305e823
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Varik, ValloHauryliuk, VVasili
By organisation
Molecular Infection Medicine Sweden (MIMS)
In the same journal
European Journal of Clinical Microbiology and Infectious Diseases
Microbiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar
Total: 22 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 24 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf