English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  This study aimed to evaluate the efficacy of combinations of steroidal alkaloids and conessine from the Thai medicinal plant  Holarrhena antidysenterica  with antibiotics against  Pseudomonas aeruginosa  strains possessing different efflux-pump-mediated multidrug-resistant (MDR) phenotypes in a  Galleria mellonella  infection model.    Methods   P. aeruginosa  strains with defined mutations that result in the overexpression of the MexAB-OprM, MexCD-OprJ and MexEF-OprN efflux pumps, and a strain with all three of these pumps deleted, were used. In vitro, the effect of combinations of steroidal alkaloids and conessine with antibiotics was compared with antibiotic treatment alone via MIC determination and time-kill assays. Efficacy of combinations of the steroidal alkaloids and conessine with levofloxacin were compared with monotherapies against infections in  G. mellonella  larvae by measuring larval mortality and bacterial burden.    Results  Combination therapies of conessine or steroidal alkaloids with levofloxacin enhanced bacterial inhibition in vitro and restored antibiotic efficacy in vivo compared to the constituent monotherapies. Neither conessine nor the steroidal alkaloids induced any detectable toxicity in  G. mellonella  larvae. The enhanced efficacy of the combination treatments was most pronounced with conessine and correlated with reduced larval burden of infecting  P. aeruginosa . Notably, the enhanced efficacy of conessine/levofloxacin combinations was only detected in the parent strain and strains that overexpressed the MexAB-OprM or MexEF-OprN efflux systems.    Conclusions  Steroidal alkaloids from  Holarrhena antidysenterica , and particularly the principal active ingredient conessine, restored levofloxacin efficacy against resistant  P. aeruginosa  strains possessing efflux-mediated MDR phenotypes. The compounds should be investigated further as a potential novel therapy.    Electronic supplementary material  The online version of this article (10.1186/s12906-018-2348-9) contains supplementary material, which is available to authorized users.

bmc complementary and alternative medicine

Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection