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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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Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae. / Perez Torres, Miquel; Entwistle, Frances; Coote, Peter John.

In: Medical Microbiology and Immunology, Vol. 205, No. 4, 08.2016, p. 333-342.

Research output: Contribution to journal › Article › peer-review

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Perez Torres, M, Entwistle, F & Coote, PJ 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

APA

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, 205(4), 333-342. https://doi.org/10.1007/s00430-016-0450-5

Vancouver

Perez Torres M, Entwistle F, Coote PJ. 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. 2016 Aug;205(4):333-342. https://doi.org/10.1007/s00430-016-0450-5

Author

Perez Torres, Miquel ; Entwistle, Frances ; Coote, Peter John. / Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae. In: Medical Microbiology and Immunology. 2016 ; Vol. 205, No. 4. pp. 333-342.

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@article{4613f80d5bde4fc19c6cd08a84104d6f,
title = "Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae",
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.",
keywords = "Insect infection model, Antibacterial, Antimicrobial, Ceftazidime, Pathogenicity, Glucocorticoid anti-inflammatory",
author = "{Perez Torres}, Miquel and Frances Entwistle and Coote, {Peter John}",
note = "MPT was the recipient of an ERASMUS training grant. FE is supported by the University of St Andrews.",
year = "2016",
month = aug,
doi = "10.1007/s00430-016-0450-5",
language = "English",
volume = "205",
pages = "333--342",
journal = "Medical Microbiology and Immunology",
issn = "0300-8584",
publisher = "Springer-Verlag",
number = "4",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae

AU - Perez Torres, Miquel

AU - Entwistle, Frances

AU - Coote, Peter John

N1 - MPT was the recipient of an ERASMUS training grant. FE is supported by the University of St Andrews.

PY - 2016/8

Y1 - 2016/8

N2 - 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.

AB - 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.

KW - Insect infection model

KW - Antibacterial

KW - Antimicrobial

KW - Ceftazidime

KW - Pathogenicity

KW - Glucocorticoid anti-inflammatory

U2 - 10.1007/s00430-016-0450-5

DO - 10.1007/s00430-016-0450-5

M3 - Article

VL - 205

SP - 333

EP - 342

JO - Medical Microbiology and Immunology

JF - Medical Microbiology and Immunology

SN - 0300-8584

IS - 4

ER -

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