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dc.contributor.authorPerez Torres, Miquel
dc.contributor.authorEntwistle, Frances
dc.contributor.authorCoote, Peter John
dc.date.accessioned2016-03-23T16:00:05Z
dc.date.available2016-03-23T16:00:05Z
dc.date.issued2016-08
dc.identifier.citationPerez Torres , M , Entwistle , F & Coote , P J 2016 , ' Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae ' Medical Microbiology and Immunology , vol. 205 , no. 4 , pp. 333-342 . https://doi.org/10.1007/s00430-016-0450-5en
dc.identifier.issn0300-8584
dc.identifier.otherPURE: 240937709
dc.identifier.otherPURE UUID: 4613f80d-5bde-4fc1-9c6c-d08a84104d6f
dc.identifier.otherScopus: 84975682948
dc.identifier.otherORCID: /0000-0001-5190-805X/work/40963219
dc.identifier.otherWOS: 000379699400005
dc.identifier.urihttp://hdl.handle.net/10023/8475
dc.descriptionMPT was the recipient of an ERASMUS training grant. FE is supported by the University of St Andrews.en
dc.description.abstractThe aim was to evaluate whether immunosuppression with dexamethasone 21-phosphate could be applied to the Galleria mellonella in vivo infection model. Characterised clinical isolates of Escherichia coli or Klebsiella pneumoniae were employed, and G. mellonella larvae were infected with increasing doses of each strain to investigate virulence in vivo. Virulence was then compared with larvae exposed to increasing doses of dexamethasone 21-phosphate. The effect of dexamethasone 21-phosphate on larval haemocyte phagocytosis in vitro was determined via fluorescence microscopy and a burden assay measured the growth of infecting bacteria inside the larvae. Finally, the effect of dexamethasone 21-phosphate treatment on the efficacy of ceftazidime after infection was also noted. The pathogenicity of K. pneumoniae or E. coli in G. mellonella larvae was dependent on high inoculum numbers such that virulence could not be attributed specifically to infection by live bacteria but also to factors associated with dead cells. Thus, for these strains, G. mellonella larvae do not constitute an ideal infection model. Treatment of larvae with dexamethasone 21-phosphate enhanced the lethality induced by infection with E. coli or K. pneumoniae in a dose- and inoculum size-dependent manner. This correlated with proliferation of bacteria in the larvae that could be attributed to dexamethasone inhibiting haemocyte phagocytosis and acting as an immunosuppressant. Notably, prior exposure to dexamethasone 21-phosphate reduced the efficacy of ceftazidime in vivo. In conclusion, demonstration of an effective immunosuppressant regimen can improve the specificity and broaden the applications of the G. mellonella model to address key questions regarding infection.
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofMedical Microbiology and Immunologyen
dc.rights© The Author(s) 2016. This article is published with open access at Springerlink.com. 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.en
dc.subjectInsect infection modelen
dc.subjectAntibacterialen
dc.subjectAntimicrobialen
dc.subjectCeftazidimeen
dc.subjectPathogenicityen
dc.subjectGlucocorticoid anti-inflammatoryen
dc.subjectQR Microbiologyen
dc.subjectQR180 Immunologyen
dc.subject.lccQRen
dc.subject.lccQR180en
dc.titleEffective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniaeen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1007/s00430-016-0450-5
dc.description.statusPeer revieweden


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