Synergistic effect of oleanolic acid on aminoglycoside antibiotics against acinetobacter baumannii

Bora Shin, Woojun Park

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Difficulties involved in treating drug-resistant pathogens have created a need for new therapies. In this study, we investigated the possibility of using oleanolic acid (OA), a natural pentacyclic triterpenoid, as a natural adjuvant for antibiotics against Acinetobacter baumannii. High concentrations of OA can kill cells, partly because it generates reactive oxygen species. Measurement of the fractional inhibitory concentration (FIC) for OA and time-kill experiments demonstrated that it only synergizes with aminoglycoside antibiotics (e.g., gentamicin, kanamycin). Other classes of antibiotics (e.g., ampicillin, rifampicin, norfloxacin, chloramphenicol, and tetracycline) have no interactions with OA. Microarray and quantitative reverse transcription-PCR analysis indicated that genes involved in ATP synthesis and cell membrane permeability, the gene encoding glycosyltransferase, peptidoglycan-related genes, phage-related genes, and DNA repair genes were upregulated under OA. OA highly induces the expression of adk, which encodes an adenylate kinase, and des6, which encodes a linoleoyl-CoA desaturase, and deletion of these genes increased FICs; these observations indicate that adk and des6 are involved in the synergism of OA with aminoglycosides. Data obtained using 8-anilino-1-naphthalenesulfonic acid, fluorescenceconjugated gentamicin, and membrane fatty acid analysis indicates that adk and des6 are involved in changes in membrane permeability. Proton-motive force and ATP synthesis tests show that those genes are also involved in energy metabolism. Taken together, our data show that OA boosts aminoglycoside uptake by changing membrane permeability and energy metabolism in A. baumannii.

Original languageEnglish
Article numbere0137751
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - 2015 Sep 11

Fingerprint

aminoglycoside antibiotics
Acinetobacter baumannii
Oleanolic Acid
oleanolic acid
Aminoglycosides
Anti-Bacterial Agents
Genes
membrane permeability
aminoglycosides
genes
gentamicin
Gentamicins
Membranes
Peptidoglycan Glycosyltransferase
energy metabolism
Energy Metabolism
Linoleoyl-CoA Desaturase
Permeability
Adenosine Triphosphate
antibiotics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Synergistic effect of oleanolic acid on aminoglycoside antibiotics against acinetobacter baumannii. / Shin, Bora; Park, Woojun.

In: PLoS One, Vol. 10, No. 9, e0137751, 11.09.2015.

Research output: Contribution to journalArticle

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