Of model hosts and man: using Caenorhabditis elegans, Drosophila melanogaster and Galleria mellonella as model hosts for infectious disease research.
ABSTRACT The use of invertebrate model hosts has increased in popularity due to numerous advantages of invertebrates over mammalian models, including ethical, logistical and budgetary features. This review provides an introduction to three model hosts, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the larvae of Galleria mellonella, the greater wax moth. It highlights principal experimental advantages of each model, for C. elegans the ability to run high-throughput assays, for D. melanogaster the evolutionarily conserved innate immune response, and for G. mellonella the ability to conduct experiments at 37°C and easily inoculate a precise quantity of pathogen. It additionally discusses recent research that has been conducted with each host to identify pathogen virulence factors, study the immune response, and evaluate potential antimicrobial compounds, focusing principally on fungal pathogens.
Article: Brain infection and activation of neuronal repair mechanisms by the human pathogen Listeria monocytogenes in the lepidopteran model host Galleria mellonella[show abstract] [hide abstract]
ABSTRACT: Listeria monocytogenes the causative agent of the foodborne disease listeriosis in humans often involves fatal brainstem infections leading to meningitis and meningoencephalitis. We recently established the larvae of the greater wax moth (Galleria mellonella) as a model host for the investigation of L. monocytogenes pathogenesis and as a source of peptides exhibiting anti-Listeria-activity. Here we show that G. mellonella can be used to study brain infection and its impact on larval development as well as the activation of stress responses and neuronal repair mechanisms. The infection of G. mellonella larvae with L. monocytogenes elicits a cellular immune response involving the formation of melanized cellular aggregates (nodules) containing entrapped bacteria. These form under the integument and in the brain, resembling the symptoms found in human patients. We screened the G. mellonella transcriptome with marker genes representing stress responses and neuronal repair, and identified several modulated genes including those encoding heat shock proteins, growth factors and regulators of neuronal stress. Remarkably, we discovered that L. monocytogenes infection leads to developmental shift in larvae and also modulates the expression of genes involved in the regulation of endocrine functions. We demonstrated that L. monocytogenes pathogenesis can be prevented by treating G. mellonella larvae with signaling inhibitors such as diclofenac, arachidonic acid and rapamycin. Our data extend the utility of G. mellonella larvae as an ideal model for the high-throughput in vivo testing of potential compounds against listeriosis.Virulence 05/2013; · 2.26 Impact Factor
Article: Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases Lifespan in Caenorhabditis elegans.[show abstract] [hide abstract]
ABSTRACT: Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3 mM and 5 mM H(2)O(2)). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans.PLoS ONE 01/2012; 7(12):e52493. · 4.09 Impact Factor
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ABSTRACT: Group A streptococcus is a strict human pathogen that can cause a wide range of diseases, such as tonsillitis, impetigo, necrotizing fasciitis, toxic shock, and acute rheumatic fever. Modeling human diseases in animals is complicated, and rapid, simple, and cost-effective in vivo models of GAS infection are clearly lacking. Recently, the use of non-mammalian models to model human disease is starting to re-attract attention. Galleria mellonella larvae, also known as wax worms, have been investigated for modeling a number of bacterial pathogens, and have been shown to be a useful model to study pathogenesis of the M3 serotype of GAS. In this study we provide further evidence of the validity of the wax worm model by testing different GAS M-types, as well as investigating the effect of bacterial growth phase and incubation temperature on GAS virulence in this model. In contrast to previous studies, we show that the M-protein, among others, is an important virulence factor that can be effectively modeled in the wax worm. We also highlight the need for a more in-depth investigation of the effects of experimental design and wax worm supply before we can properly vindicate the wax worm model for studying GAS pathogenesis.Virulence 05/2013; 4(5). · 2.26 Impact Factor