Caenorhabditis elegans as an Infection Model for Pathogenic Mold and Dimorphic Fungi: Applications and Challenges

Abstract

The threat burden from pathogenic fungi is universal and increasing with alarming high mortality and morbidity rates from invasive fungal infections. Understanding the virulence factors of these fungi, screening effective antifungal agents and exploring appropriate treatment approaches in in vivo modeling organisms are vital research projects for controlling mycoses. Caenorhabditis elegans has been proven to be a valuable tool in studies of most clinically relevant dimorphic fungi, helping to identify a number of virulence factors and immune-regulators and screen effective antifungal agents without cytotoxic effects. However, little has been achieved and reported with regard to pathogenic filamentous fungi (molds) in the nematode model. In this review, we have summarized the enormous breakthrough of applying a C. elegans infection model for dimorphic fungi studies and the very few reports for filamentous fungi. We have also identified and discussed the challenges in C. elegans-mold modeling applications as well as the possible approaches to conquer these challenges from our practical knowledge in C. elegans-Aspergillus fumigatus model.

P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata

“…We observed that Cdc50 is associated with cell wall integrity, which is of vital importance of fungal virulence; therefore, we carried out C. elegans survival assays to estimate the overall virulence of the Δcdc50 mutant in vivo. As a classical model organism that feeds on microorganisms, C. elegans is often used to evaluate the virulence of fungal and bacterial pathogens [ 44 ]. Over 300 C. elegans were transferred to plates containing medium supporting C. glabrata growth, which were incubated for at least 25 days, during which the death count of each group was recorded daily to construct the survival curve shown in Fig.…”

“…NC Negative control. *, P < 0.05; **, P < 0.01 the virulence of fungal and bacterial pathogens [44]. Over 300 C. elegans were transferred to plates containing medium supporting C. glabrata growth, which were incubated for at least 25 days, during which the death count of each group was recorded daily to construct the survival curve shown in Fig.…”

Transformation of Yeast and Mould Forms Mucor circinelloides and the Assessment of its Virulence on Galleria mellonella Larvae Model in Vivo

“…Mantarlarda dimorfizmin virülansa etkisi iyi bilinmekte (17,18) , Mucorales için dimorfizm ve virülans arasındaki ilişki de açıklanmaktadır (19) . M. circinelloides'in küf ve maya dönüşümünü belirleyen faktörler bilinmektedir.…”

“…M. circinelloides'in küf ve maya dönüşümünü belirleyen faktörler bilinmektedir. Karbon kaynağı olarak fermente edilebilir heksoz şeker var ise, maya formu gelişirken, karmaşık karbon kaynakları varlığında küf formu gelişmiştir (19) . Oksijene bağlı dimorfizm gösteren bu mantarın maya formunun elde edilmesi için anaerobik ortam koşulları oda sıcaklığı hazırlanmıştır ve 96 saat sonunda istenilen küf-maya dönüşümü gerçekleştirilmiştir.…”

Alternative Non-Mammalian Animal and Cellular Methods for the Study of Host–Fungal Interactions

“…Regarding fungi, studies have centered on nematode infections induced by dimorphic fungi, yeast-like fungi such as C. neoformans and C. albicans , and filamentous fungi like A. fumigatus and Drechmeria coniospora , which commonly inhabit natural settings [ 123 , 130 , 131 , 132 , 133 , 134 , 135 ]. Consequently, C. elegans has become an extensively explored in vivo model for investigating human infections caused by pathogens [ 123 , 124 , 135 , 136 ].…”