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Evaluation of greater wax moth larvae, Galleria mellonella, as a novel in vivo model for non-tuberculosis Mycobacteria infections and antibiotic treatments

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Date
01/04/2018
Author
Entwistle, Frances
Coote, Peter J.
Keywords
Galleria mellonella
Mycobacterium fortuitum
Mycobacterium marinum
Mycobacterium tuberculosis
Invertebrate infection model
Antibiotic susceptibility
QR Microbiology
RA0421 Public health. Hygiene. Preventive Medicine
RM Therapeutics. Pharmacology
Immunology and Microbiology(all)
NDAS
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Abstract
Purpose: To evaluate the suitability of Galleria mellonella larvae as an in vivo model and drug-screening tool for mycobacteria infections. Methodology: Larvae were infected using a range of inoculum sizes from a variety of rapid-growing mycobacteria, including strains of M. fortuitum, M. marinum and M. aurum. Larval survival, internal bacterial burden, and the effects of amikacin, ciprofloxacin, ethambutol, isoniazid and rifampicin treatment on larval survival were measured over 144h. The effects of these anti-mycobacterial drugs on phagocytosis and circulating hemocyte numbers were also examined using microscopy. Results: Larval survival decreased after infection with M. fortuitum and M. marinum in a dose-dependent manner, but remained unaffected by M. aurum. Heat-killed bacteria did not cause larval death. Where antibiotic monotherapy was efficacious, larval survival post-infection increased in a dose-dependent fashion. However, efficacy varied between different antibiotics and species of infecting mycobacteria and, apart from rifampicin, efficacy in vivo correlated poorly with the in vitro MICs. Combinations of antibiotics led to higher survival of infected larvae than antibiotic monotherapy. Selected antibiotic treatments that enhanced larval survival reduced the overall internal burden of infecting mycobacteria but did not eradicate the pathogens. Administration of amikacin or ethambutol to uninfected larvae induced an initial transient increase in the numbers of circulating hemocytes and reduced the phagocytic rate of hemocytes in larvae infected with M. marinum. Conclusions: This report demonstrates the potential of employing a wax moth larvae model for studying fast-growing mycobacteria infections, and as a cheap, effective system for initial screening of novel treatments.
Citation
Entwistle , F & Coote , P J 2018 , ' Evaluation of greater wax moth larvae, Galleria mellonella , as a novel in vivo model for non-tuberculosis Mycobacteria infections and antibiotic treatments ' , Journal of Medical Microbiology , vol. 67 , 000696 , pp. 585-597 . https://doi.org/10.1099/jmm.0.000696
Publication
Journal of Medical Microbiology
Status
Peer reviewed
DOI
https://doi.org/10.1099/jmm.0.000696
ISSN
0022-2615
Type
Journal article
Rights
© 2018, the Author(s). This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1099/jmm.0.000696
Description
Funding information: University of St Andrews.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/16240

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