Utility of Greater Wax Moth Larva (Galleria mellonella) for Evaluating the Toxicity and Efficacy of New Antimicrobial Agents

Desbois, Andrew P.; Coote, Peter J.

doi:10.1016/b978-0-12-394805-2.00002-6

Cited by 112 publications

(127 citation statements)

References 77 publications

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“…Importantly we show that G. mellonella replicates features of the pathogenesis of tuberculosis through the induction of granuloma–like structures characteristic of LTBI, and the inclusion of lipid bodies within mycobacteria over time, characteristic of persistent infection. Further evaluation of this model has the potential to markedly reduce the use of more expensive and time-consuming animal models for evaluating mycobacterial host pathogenicity, the toxicity and efficacy of novel anti-mycobacterial agents and novel vaccine candidates in vivo [66]. The characterization and optimization of this model with both non-pathogenic, and pathogenic drug-sensitive and drug-resistant M. tuberculosis isolates will form the basis of future studies.…”

Section: Discussionmentioning

confidence: 99%

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

Spiropoulos

Cooley

et al. 2018

Virulence

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Animal models have long been used in tuberculosis research to understand disease pathogenesis and to evaluate novel vaccine candidates and anti-mycobacterial drugs. However, all have limitations and there is no single animal model which mimics all the aspects of mycobacterial pathogenesis seen in humans. Importantly mice, the most commonly used model, do not normally form granulomas, the hallmark of tuberculosis infection. Thus there is an urgent need for the development of new alternative in vivo models. The insect larvae, Galleria mellonella has been increasingly used as a successful, simple, widely available and cost-effective model to study microbial infections. Here we report for the first time that G. mellonella can be used as an infection model for members of the Mycobacterium tuberculosis complex. We demonstrate a dose-response for G. mellonella survival infected with different inocula of bioluminescent Mycobacterium bovis BCG lux, and demonstrate suppression of mycobacterial luminesence over 14 days. Histopathology staining and transmission electron microscopy of infected G. mellonella phagocytic haemocytes show internalization and aggregation of M. bovis BCG lux in granuloma-like structures, and increasing accumulation of lipid bodies within M. bovis BCG lux over time, characteristic of latent tuberculosis infection. Our results demonstrate that G. mellonella can act as a surrogate host to study the pathogenesis of mycobacterial infection and shed light on host-mycobacteria interactions, including latent tuberculosis infection.

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Section: Discussionmentioning

confidence: 99%

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

Spiropoulos

Cooley

et al. 2018

Virulence

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“…The insect immune system shows many similarities to the innate immune system of mammals (Kavanagh and Reeves 2004;Browne et al 2013) and, as a consequence, insects have been used as models to measure the virulence of microbial pathogens (Fuchs and Mylonakis 2006) and to evaluate the potency of antimicrobial drugs (Hamamoto et al 2004;Rowan et al 2009) and give results consistent with those that can be obtained using mammals (Jander et al 2000;Brennan et al 2002). A number of insect species can be employed for evaluating the in vivo activity of novel antimicrobial drugs (Kavanagh and Fallon 2010) and larvae of the Greater Wax Moth, Galleria mellonella are now widely used in this capacity (Kelly and Kavanagh 2011;Rowan et al 2009;Desbois and Coote 2012). This paper describes the antimicrobial effects of SBC3 against the bacterium S. aureus and the yeast Candida albicans in vitro and demonstrates the in vivo activity and toxicity of SBC3 against these two pathogens in G. mellonella larvae.…”

Section: Introductionmentioning

confidence: 99%

Assessment of in vivo antimicrobial activity of the carbene silver(I) acetate derivative SBC3 using Galleria mellonella larvae

et al. 2014

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The antimicrobial drug candidate 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate (SBC3) was evaluated for its ability to function in vivo using larvae of Galleria mellonella. A SBC3 concentration of 25 lg/ml inhibited the growth of Staphylococcus aureus by 71.2 % and Candida albicans by 86.2 % in vitro. Larvae inoculated with 20 ll of SBC3 solution showed no ill effects up to a concentration of 250 lg/ml but administration of 500 lg/ml resulted in a 40 % reduction in larval survival and administration of a dose of 1,000 lg/ml resulted in total larval death at 24 h. Larvae inoculated with S. aureus or C. albicans and subsequently administered SBC3 showed increased survival. Administration of SBC3 to larvae did not boost the insect immune response as indicated by lack of an increase in the density of circulating haemocytes (immune cells). The abundance of a number of proteins involved in the insect immune response was reduced in larvae that received 20 ll SBC3 solution of 100 lg/ml. This is the first demonstration of the in vivo activity of SBC3 against S. aureus and C. albicans and demonstrates that SBC3 does not stimulate a non-specific immune response in larvae.

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“…Such larvae have been widely used as a convenie nt and inexpensive in vivo screening model to assess the toxicity of potential new drugs [11,12]. Ten healthy larvae, weighing between 0.2-0.4 g and with no cuticle discolourati on, were used for each compound.…”

Section: In Vivo Toxicity Assessmen Tmentioning

confidence: 99%

Imidazole Schiff base ligands: Synthesis, coordination complexes and biological activities

McGinley¹,

McCann²,

Ni³

et al. 2013

Polyhedron

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a b s t r a c t 1-(3-Aminopropyl)imidazole (Apim) reacts with salicylaldeh yde and a selection of imidazole aldehydes and the resulting Schiff base ligands readily coordinate to Zn(II), Cu(II) and Ag(I) centres. X-ray crystal structures were obtained for two of the free ligands and also the Ag(I) complex of the Apim-salicylaldehyde ligand. Encouragingly, all of free ligands and most of their metal complexes are relatively non-toxic, in vivo , towards Galleria mellonella . Although the free ligands and the Cu(II) and Zn(II) complexes are inactive, in vitro , against a selection of microbial pathogens, most of the Ag(I) complexes exhibit moderate anti-bacterial activity and good anti-fungal activity.

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Utility of Greater Wax Moth Larva (Galleria mellonella) for Evaluating the Toxicity and Efficacy of New Antimicrobial Agents

Cited by 112 publications

References 77 publications

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

Assessment of in vivo antimicrobial activity of the carbene silver(I) acetate derivative SBC3 using Galleria mellonella larvae

Imidazole Schiff base ligands: Synthesis, coordination complexes and biological activities

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