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Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae

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Date
08/2016
Author
Perez Torres, Miquel
Entwistle, Frances
Coote, Peter John
Keywords
Insect infection model
Antibacterial
Antimicrobial
Ceftazidime
Pathogenicity
Glucocorticoid anti-inflammatory
QR Microbiology
QR180 Immunology
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Abstract
The 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.
Citation
Perez 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/s00430-016-0450-5
Publication
Medical Microbiology and Immunology
Status
Peer reviewed
DOI
https://doi.org/10.1007/s00430-016-0450-5
ISSN
0300-8584
Type
Journal article
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.
Description
MPT was the recipient of an ERASMUS training grant. FE is supported by the University of St Andrews.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/8475

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