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dc.contributor.authorSiriyong, Thanyaluck
dc.contributor.authorVoravuthikunchai, Supayang Piyawan
dc.contributor.authorCoote, Peter John
dc.identifier.citationSiriyong , T , Voravuthikunchai , S P & Coote , P J 2018 , ' Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection ' , BMC Complementary and Alternative Medicine , vol. 18 , 285 .
dc.identifier.otherPURE: 256155647
dc.identifier.otherPURE UUID: 0db0517e-0904-4895-99fb-96dc14da13d4
dc.identifier.otherScopus: 85055072188
dc.identifier.otherORCID: /0000-0001-5190-805X/work/49580172
dc.identifier.otherWOS: 000447743800003
dc.descriptionThis work was supported by the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0041/2556) co-funded by the Newton Fund of the British Council and TRF Senior Research Scholar (Grant No. RTA 5880005).en
dc.description.abstractBackground 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.
dc.relation.ispartofBMC Complementary and Alternative Medicineen
dc.rights© The Author(s). 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.en
dc.subjectEfflux pump inhibitoren
dc.subjectGalleria mellonellaen
dc.subjectHolarrhena antidysentericaen
dc.subjectMex efflux systemsen
dc.subjectRV Botanic, Thomsonian, and eclectic medicineen
dc.titleSteroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infectionen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.description.statusPeer revieweden

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