Fungal immunity and pathogenesis in mammals versus the invertebrate model organism<i>Galleria mellonella</i>

Smith, Daniel F. Q.; Casadevall, Arturo

doi:10.1093/femspd/ftab013

Cited by 26 publications

(13 citation statements)

References 308 publications

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“…Larvae exhibit a humoral immune response to microbial infections and the activation of specific immune cells that is similar to the innate immune response in murine models [39]. G. mellonella innate systems include pattern recognition receptors to recognize microbial invasion and phagocytic cells like plasmatocytes and hemocytes to prevent colonization and infection (reviewed by Smith and Casadevall [40]). Reported data indicate that fungal virulence factors have comparable immune function roles in mammalian and G. mellonella hosts, suggesting that G. mellonella studies can be translatable to mammals [40].…”

Section: Discussionmentioning

confidence: 99%

“…G. mellonella innate systems include pattern recognition receptors to recognize microbial invasion and phagocytic cells like plasmatocytes and hemocytes to prevent colonization and infection (reviewed by Smith and Casadevall [40]). Reported data indicate that fungal virulence factors have comparable immune function roles in mammalian and G. mellonella hosts, suggesting that G. mellonella studies can be translatable to mammals [40]. Galleria larvae can grow under versatile conditions, making them an excellent model for research on Coccidioides.…”

Section: Discussionmentioning

confidence: 99%

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Galleria mellonella Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification

Mendoza Barker,

Saeger,

Campuzano

et al. 2024

JoF

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Coccidioidomycosis (CM) can manifest as respiratory and disseminated diseases that are caused by dimorphic fungal pathogens, such as Coccidioides species. The inhaled arthroconidia generated during the saprobic growth phase convert into multinucleated spherules in the lungs to complete the parasitic lifecycle. Research on coccidioidal virulence and pathogenesis primarily employs murine models typically associated with low lethal doses (LD100 < 100 spores). However, the Galleria model has recently garnered attention due to its immune system bearing both structural and functional similarities to the innate system of mammals. Our findings indicate that Coccidioides posadasii can convert and complete the parasitic cycle within the hemocoel of the Galleria larva. In Galleria, the LD100 is between 0.5 and 1.0 × 106 viable spores for the clinical isolate Coccidioides posadasii C735. Furthermore, we demonstrated the suitability of this model for in vivo antifungal susceptibility tests to validate the bioreactivity of newly discovered antifungals against Coccidioides. Additionally, we utilized this larva model to screen a Coccidioides posadasii mutant library showing attenuated virulence. Similarly, the identified attenuated coccidioidal mutants displayed a loss of virulence in a commonly used murine model of coccidioidomycosis. In this study, we demonstrated that Galleria larvae can be applied as a model for studying Coccidioides infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Galleria mellonella Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification

Mendoza Barker,

Saeger,

Campuzano

et al. 2024

JoF

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“…In contrast to mammals, G. mellonella has phenol oxidase that produces melanin from tyrosine as antimicrobial strategy to kill pathogens. 30 F I G U R E 6 Effect of antifungal compounds against Candida albicans biofilm implant infection in Galleria mellonella. We tested amphotericin B, fluconazole, and voriconazole compounds against C. albicans infection.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the evolutionary distance to mammals, the G. mellonella immune system is broadly similar to the innate immune system of mammals and consists of pattern recognition receptors, a complement‐like system and hemocytes as phagocytic cells to eliminate pathogens. In contrast to mammals, G. mellonella has phenol oxidase that produces melanin from tyrosine as antimicrobial strategy to kill pathogens 30 . C‐type lectin receptors (CLRs) play a major role in the antifungal defense by attaching to fungal cell wall carbohydrates, such as mannans and glucans.…”

Section: Discussionmentioning

confidence: 99%

Galleria mellonella as an alternative in vivo model to study implant‐associated fungal infections

Mannala

Rupp

Walter

et al. 2023

Journal Orthopaedic Research

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Fungal implant‐associated bone infections are rare but difficult to treat and often associated with a poor outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play a major role to study biofilm development and potential new treatment options; however, there are only a very few in vivo models to study fungi‐associated biofilms. Furthermore, mammalian infection models are replaced more and more due to ethical restrictions with other alternative models in basic research. Recently, we developed an insect infection model with Galleria mellonella larvae to study biofilm‐associated infections with bacteria. Here, we further expanded the G. mellonella model to study in vivo fungal infections using Candida albicans and Candida krusei. We established a planktonic and biofilm‐implant model to test different antifungal medication with amphotericin B, fluconazole, and voriconazole against the two species and assessed the fungal biofilm‐load on the implant surface. Planktonic infection with C. albicans and C. krusei showed the killing of the G. mellonella larvae at 5 × 105 colony forming units (CFU). Treatment of larvae with antifungal compounds with amphotericin B and fluconazole showed significant survival improvement against planktonic C. albicans infection, but voriconazole had no effect. Titanium and stainless steel K‐wires were preincubated with C. albicans and implanted inside the larvae to induce biofilm infection on the implant surface. The survival analysis revealed significantly reduced survival of the larvae with Candida spp. infection compared to noninfected implants. The treatment with antifungal amphotericin B and fluconazole resulted in a slight and nonsignificant improvement survival of the larvae. The treatment with the antifungal compounds in the biofilm‐infection model was not as effective as in the planktonic infection model, which highlights the resistance of fungal biofilms to antifungal compounds like in bacterial biofilms. Scanning electron microscopy (SEM) analysis revealed the formation of a fungal biofilm with hyphae and spores associated with larvae tissue on the implant surface. Thus, our study highlights the use of G. mellonella larvae as alternative in vivo model to study biofilm‐associated implant fungal infections and that fungal biofilms exhibit high resistance profiles comparable to bacterial biofilms. The model can be used in the future to test antifungal treatment options for fungal biofilm infections.

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“…In our study, the importance of A. fumigatus Nmo2 and Nmo5 for virulence was shown using in vitro macrophage and in vivo G. mellonella infection models. Although G. mellonella has been proven as a useful model to study fungal virulence, its drawbacks include evolutionary genetic divergence between mammals and insects, and the lack of an equivalent to the mammalian adaptive immune response [ 43 ]. In future studies, virulence assessments should, therefore, be carried out with different models, such as murine models.…”

Section: Discussionmentioning

confidence: 99%

Understanding the Role of Nitronate Monooxygenases in Virulence of the Human Fungal Pathogen Aspergillus fumigatus

Nguyen

Wacker

Brown

et al. 2022

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Aspergillus fumigatus is the leading cause of the fungal invasive disease called aspergillosis, which is associated with a high mortality rate that can reach 50% in some groups of immunocompromised individuals. The increasing prevalence of azole-resistant A. fumigatus isolates, both in clinical settings and the environment, highlights the importance of discovering new fungal virulence factors that can potentially become targets for novel antifungals. Nitronate monooxygenases (Nmos) represent potential targets for antifungal compounds as no orthologs of those enzymes are present in humans. Nmos catalyse the denitrification of nitroalkanes, thereby detoxifying these mediators of nitro-oxidative stress, and therefore we tested whether Nmos provide protection for A. fumigatus against host-imposed stresses at sites of infection. The results of inhibition zone assays indicated that Nmo2 and Nmo5 are not essential for the oxidative stress resistance of A. fumigatus in vitro. In addition, the resazurin-based metabolic activity assay revealed that the growth of mutants lacking the nmo2 or nmo5 genes was only slightly reduced in the presence of 0.05 mM peroxynitrite. Nevertheless, both Nmo2 and Nmo5 were shown to contribute to defense against murine bone marrow-derived macrophages, and this was no longer observed when NADPH oxidase, the main generator of reactive oxygen species during infection, was inhibited in macrophages. Furthermore, we revealed that Nnmos promote the virulence of the fungus in the Galleria mellonella model of infection. Both nmo2 and nmo5 knock-out strains were less virulent than the wild-type control as recorded 72 h post-infection. Our results indicate that Nmos play a role in the virulence of A. fumigatus.

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Fungal immunity and pathogenesis in mammals versus the invertebrate model organismGalleria mellonella

Cited by 26 publications

References 308 publications

Galleria mellonella Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification

Galleria mellonella Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification

Galleria mellonella as an alternative in vivo model to study implant‐associated fungal infections

Understanding the Role of Nitronate Monooxygenases in Virulence of the Human Fungal Pathogen Aspergillus fumigatus

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