Evaluation of the efficacy of antifungal drugs against Paracoccidioides brasiliensis and Paracoccidioides lutzii in a Galleria mellonella model

Singulani, Júnya de Lacorte; Scorzoni, Liliana; Silva, Ana Carolina Alves de Paula e; Fusco‐Almeida, Ana Marisa; Mendes-Giannini, María José Soares

doi:10.1016/j.ijantimicag.2016.05.012

Cited by 21 publications

(26 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The benefit of this is that the inoculum and the treatment are controlled. G. mellonella is useful for in vivo treatment with conventional antifungal drugs (Coleman et al, 2011; de Lacorte Singulani et al, 2016), for assessing antifungal synergistic activity (Gu et al, 2016; Sangalli-Leite et al, 2016) and for evaluating the in vivo efficacy of new drug candidates (Browne et al, 2014). …”

Section: Alternative Animal Models To Study Fungal Virulence and Antimentioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

Self Cite

View full text Add to dashboard Cite

The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of eﬄux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the preliminary testing of new antifungal agents. In general, many years are required from discovery of a new antifungal to clinical use. However, the development of new antifungal strategies will reduce the therapeutic time and/or increase the quality of life of patients.

show abstract

Section: Alternative Animal Models To Study Fungal Virulence and Antimentioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…[32,33,[45][46][47][48][49][50][51], Aspergillus spp. [13,29,35,[52][53][54][55][56][57][58][59][60][61], Mucorales [62][63][64], Madurella mycetomatis [65][66][67], and other fungal agents [68][69][70]. The contribution of G. mellonella to the evaluation of antifungal drugs will be detailed in the following paragraphs.…”

Section: Evaluation Of Antifungal Efficacy In Galleria Mellonellamentioning

confidence: 99%

Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review

et al. 2020

View full text Add to dashboard Cite

The treatment of invasive fungal infections remains challenging and the emergence of new fungal pathogens as well as the development of resistance to the main antifungal drugs highlight the need for novel therapeutic strategies. Although in vitro antifungal susceptibility testing has come of age, the proper evaluation of therapeutic efficacy of current or new antifungals is dependent on the use of animal models. Mammalian models, particularly using rodents, are the cornerstone for evaluation of antifungal efficacy, but are limited by increased costs and ethical considerations. To circumvent these limitations, alternative invertebrate models, such as Galleria mellonella, have been developed. Larvae of G. mellonella have been widely used for testing virulence of fungi and more recently have proven useful for evaluation of antifungal efficacy. This model is suitable for infection by different fungal pathogens including yeasts (Candida, Cryptococcus, Trichosporon) and filamentous fungi (Aspergillus, Mucorales). Antifungal efficacy may be easily estimated by fungal burden or mortality rate in infected and treated larvae. The aim of the present review is to summarize the actual data about the use of G. mellonella for testing the in vivo efficacy of licensed antifungal drugs, new drugs, and combination therapies.

show abstract

“…Among these alternative models, the Galleria mellonella model is gaining popularity because, unlike other non-mammal models, it allows for both, toxicity and antimicrobial activity testing [8][9][10][11][12][13][14]. This is due to the fact that larvae survive at 37°C [15].…”

Section: Introductionmentioning

confidence: 99%

New solvent options for in vivo assays in the Galleria mellonella larvae model

et al. 2019

View full text Add to dashboard Cite

Experimentation in mammals is a long and expensive process in which ethical aspects must be considered, which has led the scientific community to develop alternative models such as that of Galleria mellonella. This model is a cost and time effective option to act as a filter in the drug discovery process. The main limitation of this model is the lack of variety in the solvents used to administer compounds, which limits the compounds that can be studied using this model. Five aqueous (DMSO, MeOH, acetic acid, HCl and NaOH) and four non-aqueous (olive oil, isopropyl myristate, benzyl benzoate and ethyl oleate) solvents was assessed to be used as vehicles for toxicity and antimicrobial activity in vivo assays. All the tested solvents were innocuous at the tested concentrations except for NaOH, which can be used at a maximum concentration of 0.5 M. The toxicity of two additional compounds, 5-aminosalicylic acid and DDT, was also assessed. The results obtained allow for the testing of a broader range of compounds using wax moth larvae. This model appears as an alternative to mammal models, by acting as a filter in the drug development process and reducing costs and time invested in new drugs.

show abstract

Evaluation of the efficacy of antifungal drugs against Paracoccidioides brasiliensis and Paracoccidioides lutzii in a Galleria mellonella model

Cited by 21 publications

References 38 publications

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review

New solvent options for in vivo assays in the Galleria mellonella larvae model

Contact Info

Product

Resources

About