Using &lt;i&gt;Galleria mellonella&lt;/i&gt;–&lt;i&gt;Candida albicans&lt;/i&gt; Infection Model to Evaluate Antifungal Agents

Li, Dedong; Deng, Li; Hu, Guang; Zhao, Lijie; Hu, Dandan; Jiang, Yuanying; Wang, Yan

doi:10.1248/bpb.b13-00270

Cited by 75 publications

(67 citation statements)

References 21 publications

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“…G. mellenella larvae have been used to study antibiotic treatment for different bacterial and fungal infections [27, 35, 36]. To assess the utility of G. mellonella larvae to study antibacterial therapies against S. suis , we confirmed that antibiotic therapy could rescue larvae from S. suis infection.…”

Section: Resultsmentioning

confidence: 58%

Evaluation of Galleria mellonella larvae for studying the virulence of Streptococcus suis

2016

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Background Streptococcus suis is an encapsulated Gram-positive bacterium and the leading cause of sepsis and meningitis in young pigs, resulting in considerable economic losses in the porcine industry. S. suis is considered an emerging zoonotic agent with increasing numbers of human cases over the last years. In the environment, both avirulent and virulent strains occur in pigs, with no evidence for consistent adapatation of virulent strains to the human host. Currently, there is an urgent need for a convenient, reliable and standardised animal model to rapidly assess S. suis virulence. Wax moth (Galleria mellonella) larvae have successfully been used in human and animal infectious disease studies. Here, we developed G. mellonella larvae as a model to assess virulence of S. suis strains.ResultsFourteen isolates of S. suis belonging to different serotypes killed G. mellonella larvae in a dose-dependent manner. Larvae infected with the virulent serotype 2 strain, S. suis S3881/S10, were rescued by antibiotic therapy. Crucially, the observed virulence of the different serotypes and mutants was in agreement with virulence observed in piglets (Sus scrofa) and the zebrafish larval infection model. Infection with heat-inactivated bacteria or bacteria-free culture supernatants showed that in most cases live bacteria are needed to cause mortality in G. mellonella.ConclusionsThe G. mellonella model is simple, cost-efficient, and raises less ethical issues than experiments on vertebrates and reduces infrastructure requirements. Furthermore, it allows experiments to be performed at the host temperature (37 °C). The results reported here, indicate that the G. mellonella model may aid our understanding of veterinary microbial pathogens such as the emerging zoonotic pathogen S. suis and generate hypotheses for testing in the target animal host. Ultimately, this might lead to the timely introduction of new effective remedies for infectious diseases. Last but not least, use of the G. mellonella infection model to study S. suis virulence adheres to the principles of replacement, reduction and refinement (3Rs) and can potentially reduce the number of vertebrates used for experimental infection studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0905-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 58%

Evaluation of Galleria mellonella larvae for studying the virulence of Streptococcus suis

2016

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“…41,42 A high dose of FLC or VRC was able to improve the survival of the animals compared to the untreated control groups infected with any of the 3 Trichosporon species, while AMB was not able to reduce mortality in any of the 3 species (Fig. 4).…”

Section: Galleria Mellonella Virulence Modelmentioning

confidence: 97%

The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

et al. 2015

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The present study developed Galleria mellonella and murine infection models for the study of Trichosporon infections. The utility of the developed animal models was demonstrated through the assessment of virulence and antifungal efficacy for 7 clinical isolates of Trichosporon asahii, T. asteroides and T. inkin. The susceptibility of the Trichosporon isolates to several common antifungal drugs was tested in vitro using the broth microdilution and the Etest methods. The E-test method depicted a lower minimal inhibitory concentration (MIC) for amphotericin and a slightly higher MIC for caspofungin, while MICs observed for the azoles were different but comparable between both methods. All three Trichosporon species established infection in both the G. mellonella and immunosuppressed murine models. Species and strain dependent differences were observed in both the G. mellonella and murine models. T. asahii was demonstrated to be more virulent than the other 2 species in both animal hosts. Significant differences in virulence were observed between strains for T. asteroides in the murine model. In both animal models, fluconazole and voriconazole were able to improve the survival of the animals compared to the untreated control groups infected with any of the 3 Trichosporon species. In G. mellonella, amphotericin was not able to reduce mortality in any of the 3 species. In contrast, amphotericin was able to reduce murine mortality in the T. asahii or T. inkin models, respectively. Hence, the developed animal infection models can be directly applicable to the future deeper investigation of the molecular determinants of Trichosporon virulence and antifungal resistance.

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“…On the other hand, the C. elegans model has also often been used in the screening and development of new antifungal chemical compounds [81], to study Candida virulence factors [68], and to examine antifungal innate immunity [82]. Like the D. melanogaster and C. elegans models, the G. mellonella model has been employed in many studies, including experiments on Candida albicans mutants and virulence [83,84], Candida virulence factors [85,86,87], C. albicans virulence transcriptional factors [88], photodynamic therapy (PDT) as a treatment regimen for Candida infections [89], and the evaluation of the efficacy of antifungal agents [90]. Overall, the adoption of these mini-hosts in C. albicans infection studies provides a number of advantages.…”

Section: C Albicans Infection In Animal Modelsmentioning

confidence: 99%

Dissecting Candida albicans Infection from the Perspective of C. albicans Virulence and Omics Approaches on Host–Pathogen Interaction: A Review

Chin

Lee

Basir

et al. 2016

IJMS

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Candida bloodstream infections remain the most frequent life-threatening fungal disease, with Candida albicans accounting for 70% to 80% of the Candida isolates recovered from infected patients. In nature, Candida species are part of the normal commensal flora in mammalian hosts. However, they can transform into pathogens once the host immune system is weakened or breached. More recently, mortality attributed to Candida infections has continued to increase due to both inherent and acquired drug resistance in Candida, the inefficacy of the available antifungal drugs, tedious diagnostic procedures, and a rising number of immunocompromised patients. Adoption of animal models, viz. minihosts, mice, and zebrafish, has brought us closer to unraveling the pathogenesis and complexity of Candida infection in human hosts, leading towards the discovery of biomarkers and identification of potential therapeutic agents. In addition, the advancement of omics technologies offers a holistic view of the Candida-host interaction in a non-targeted and non-biased manner. Hence, in this review, we seek to summarize past and present milestone findings on C. albicans virulence, adoption of animal models in the study of C. albicans infection, and the application of omics technologies in the study of Candida–host interaction. A profound understanding of the interaction between host defense and pathogenesis is imperative for better design of novel immunotherapeutic strategies in future.

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Using <i>Galleria mellonella</i>–<i>Candida albicans</i> Infection Model to Evaluate Antifungal Agents

Cited by 75 publications

References 21 publications

Evaluation of Galleria mellonella larvae for studying the virulence of Streptococcus suis

Evaluation of Galleria mellonella larvae for studying the virulence of Streptococcus suis

The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

Dissecting Candida albicans Infection from the Perspective of C. albicans Virulence and Omics Approaches on Host–Pathogen Interaction: A Review

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