Identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis

Yaakov, Dafna Ben; Rivkin, Anna; Mircus, Gabriel; Albert, Nathaniel D.; Dietl, Anna Maria; Kovalerchick, Dimitry; Carmeli, Shmuel; Haas, Hubertus; Kontoyiannis, Dimitrios P.; Osherov, Nir

doi:10.1093/jac/dkv446

Cited by 25 publications

(20 citation statements)

References 19 publications

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“…[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%

“…The treatment of G. mellonella infected with Aspergillus spp. has been evaluated in several studies (Table 4) in order to assess intrinsic resistance in specific species [55,56,83], acquired azole resistance in A. fumigatus [53,54], combinations [35,59], and efficacy of non-antifungal drugs [29,57,58,60,61]. A. fumigatus VRZ (10) AMB (3) sertraline (3,10)…”

Section: Aspergillus Sppmentioning

confidence: 99%

“…mellonella has also been used as an in vivo model for the evaluation of antifungal efficacy of new drugs [57,58,60] or in the context of repurposing [29,61]. By screening large chemical libraries, several drugs with promising antifungal activity were identified and further tested in animal models, including G. mellonella [57,58,60]. Bromoquinol, a quinoline, showed efficacy similar to that of the amphotericin B used as a positive control [58].…”

Section: Nomentioning

confidence: 99%

“…While amphotericin B was effective compared to controls, bromoquinol did not significantly improve survival of infected mice. Another compound with activity at the cell wall level, called haemafungin, was tested in G. mellonella for its antifungal efficacy [57]. In larvae inoculated with a lethal dose of A. fumigatus, haemofungin had a similar efficacy to amphotericin B.…”

Section: Nomentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Evaluation Of Antifungal Efficacy In Galleria Mellonellamentioning

confidence: 99%

Section: Aspergillus Sppmentioning

confidence: 99%

Section: Nomentioning

confidence: 99%

Section: Nomentioning

confidence: 99%

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

et al. 2020

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“…In larvae, haemofungin is non-toxic up to 22.7 mg/kg. Most interestingly, a concentration of 5.7 mg/kg haemofungin improved larval survival to A. fumigatus comparable to that of amphotericin (2 mg/kg) [ 63 ].…”

Section: Use Of Larvae For Assessing Antifungal Activity In Vivomentioning

confidence: 99%

The Use of Galleria mellonella Larvae to Identify Novel Antimicrobial Agents against Fungal Species of Medical Interest

Kavanagh

Sheehan

2018

JoF

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The immune system of insects and the innate immune response of mammals share many similarities and, as a result, insects may be used to assess the virulence of fungal pathogens and give results similar to those from mammals. Larvae of the greater wax moth Galleria mellonella are widely used in this capacity and also for assessing the toxicity and in vivo efficacy of antifungal drugs. G. mellonella larvae are easy to use, inexpensive to purchase and house, and have none of the legal/ethical restrictions that are associated with use of mammals. Larvae may be inoculated by intra-hemocoel injection or by force-feeding. Larvae can be used to assess the in vivo toxicity of antifungal drugs using a variety of cellular, proteomic, and molecular techniques. Larvae have also been used to identify the optimum combinations of antifungal drugs for use in the treatment of recalcitrant fungal infections in mammals. The introduction of foreign material into the hemocoel of larvae can induce an immune priming effect which may operate independently with the activity of the antifungal drug. Procedures to identify this effect and limit its action are required.

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Updates on the Treatment of Non-Aspergillus Hyaline Mold Infections

Nematollahi

Shoham

2019

Curr Fungal Infect Rep

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Identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis

Abstract: Further development and in vivo validation of haemofungin is warranted.

Cited by 25 publications

References 19 publications

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

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

The Use of Galleria mellonella Larvae to Identify Novel Antimicrobial Agents against Fungal Species of Medical Interest

Updates on the Treatment of Non-Aspergillus Hyaline Mold Infections

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