Abstract
There is an urgent need for new antimicrobial agents to combat
infections caused by drug-resistant pathogens. Once a compound is
shown to be effective in vitro, it is necessary to evaluate its efficacy
in an animal infection model. Typically, this is achieved using a
mammalian model, but such experiments are costly, time consuming,
and require full ethical consideration. Hence, cheaper and
ethically more acceptable invertebrate models of infection have been introduced, including the larvae of the greater wax moth
Galleria mellonella. Invertebrates have an immune system that is
functionally similar to the innate immune system of mammals, and
often identical virulence and pathogenicity factors are used by
human pathogenic microbes to infect wax moth larvae and mammals.
Moreover, the virulence of many human pathogens is comparable
in wax moth larvae and mammals. Using key examples from
the literature, this chapter highlights the benefits of using the wax
moth larva model to provide a rapid, inexpensive, and reliable
evaluation of the toxicity and efficacy of new antimicrobial agents
in vivo and prior to the use of more expensive mammalian models.
This simple insect model can bridge the gap between in vitro
studies and mammalian experimentation by screening out compounds
with a low likelihood of success, while providing greater
justification for further studies in mammalian systems. Thus,
broader implementation of the wax moth larva model into antiinfective
drug discovery and development programs could reduce
the use of mammals during preclinical assessments and the overall
cost of drug development.
infections caused by drug-resistant pathogens. Once a compound is
shown to be effective in vitro, it is necessary to evaluate its efficacy
in an animal infection model. Typically, this is achieved using a
mammalian model, but such experiments are costly, time consuming,
and require full ethical consideration. Hence, cheaper and
ethically more acceptable invertebrate models of infection have been introduced, including the larvae of the greater wax moth
Galleria mellonella. Invertebrates have an immune system that is
functionally similar to the innate immune system of mammals, and
often identical virulence and pathogenicity factors are used by
human pathogenic microbes to infect wax moth larvae and mammals.
Moreover, the virulence of many human pathogens is comparable
in wax moth larvae and mammals. Using key examples from
the literature, this chapter highlights the benefits of using the wax
moth larva model to provide a rapid, inexpensive, and reliable
evaluation of the toxicity and efficacy of new antimicrobial agents
in vivo and prior to the use of more expensive mammalian models.
This simple insect model can bridge the gap between in vitro
studies and mammalian experimentation by screening out compounds
with a low likelihood of success, while providing greater
justification for further studies in mammalian systems. Thus,
broader implementation of the wax moth larva model into antiinfective
drug discovery and development programs could reduce
the use of mammals during preclinical assessments and the overall
cost of drug development.
Original language | English |
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Title of host publication | Advances in Applied Microbiology |
Editors | Allen I. Laskin, Sima Sariaslani, Geoffrey M Gadd |
Place of Publication | San Diego |
Publisher | Elsevier |
Pages | 25-53 |
Number of pages | 29 |
Volume | 78 |
ISBN (Print) | 978-0-12-394805-2 |
DOIs | |
Publication status | Published - 2012 |
Keywords
- IMMUNE-RESPONSE
- CAENORHABDITIS-ELEGANS
- FUNGAL PATHOGENESIS
- ALTERNATIVE INFECTION MODEL
- GROUP-A STREPTOCOCCUS
- BACILLUS-CEREUSFUNGAL PATHOGENESIS
- BURKHOLDERIA-CEPACIA COMPLEX
- IN-VIVO
- INSECT MODEL
- CANDIDA-ALBICANS