Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis , and Candida bracarensis Virulence and Antifungal Efficacy

Abstract

Although Candida albicans remains the major etiological agent of invasive candidiasis, Candida glabrata and other emerging species of Candida are increasingly isolated. This species is the second most prevalent cause of candidiasis in many regions of the world. However, clinical isolates of Candida nivariensis and Candida bracarensis can be misidentified and are underdiagnosed due to shared phenotypic traits with C. glabrata. Little is known about both cryptic species. Pathogenesis studies are therefore needed to understand their virulence traits and their susceptibility to antifungal drugs. The susceptibility of Caenorhabditis elegans to different Candida species makes this nematode an excellent model for assessing host–fungal interactions. We evaluated the usefulness of C. elegans as a nonconventional host model to analyze the virulence of C. glabrata, C. nivariensis and C. bracarensis. The three species caused candidiasis and the highest virulence of C. glabrata was confirmed. Furthermore, we determined the efficacy of current antifungal drugs against the infection caused by these species in the C. elegans model. Amphotericin B and azoles showed the highest activity against C. glabrata and C. bracarensis infections, while echinocandins were more active for treating those caused by C. nivariensis. C. elegans proved to be a useful model system for assessing the pathogenicity of these closely related species.

Virulence ofCandida aurisfrom different clinical origins inCaenorhabditis elegansandGalleria mellonellahost models

“…These results are comparable to those obtained in other studies, which observed that C. auris caused death of G. mellonella within 48 h [ 21 , 22 ] and of C. elegans between 48 and 96 h post-infection [ 23 , 29 ]. Our findings corroborate the idea that both models successfully demonstrate the virulence potential of C. auris , which was similar to or higher than that of other Candida species [ 11 , 30 , 32 , 33 , 52 ]. The observed virulence of C. auris was comparable to C. albicans [ 21 , 22 , 29 ] and higher than isolates from C. haemulonii complex species [ 11 , 29 ].…”

Candida glabrata Antifungal Resistance and Virulence Factors, a Perfect Pathogenic Combination

“…Reports indicate that in the same way there are differences in the virulence factors among the C. glabrata complex species, there are also differences in their antifungal resistance. For example, reports show that C. glabrata sensu stricto is more susceptible to fluconazole, itraconazole, and voriconazole than C. nivariensis [ 62 , 63 , 92 ].…”

“…However, due to the difficulty differentiating them from C. glabrata sensu stricto , the clinical significance and actual prevalence of C. nivariensis and C. bracarensis have been underestimated. The latter affects their treatment, as they exhibit greater resistance to azoles and echinocandins [ 57 , 58 , 61 , 62 , 63 , 64 ]. It should be noted that the increasing use of azole antifungals for the treatment of superficial and systemic infections by Candida glabrata has led to the selection and emergence of resistant isolates, as well as increased infections by other non- albicans species [ 57 ].…”

“…It should be noted that the increasing use of azole antifungals for the treatment of superficial and systemic infections by Candida glabrata has led to the selection and emergence of resistant isolates, as well as increased infections by other non- albicans species [ 57 ]. Besides, it is considered that C. glabrata sensu stricto is the most virulent species, followed by C. nivariensis and C. bracarensis [ 62 , 63 ].…”

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

“…The in vivo efficacy of known antifungal drugs and a number of repurposed drugs have also been applied in the treatment of nematode candidiasis. Several azoles (Souza et al, 2018;Hernando-Ortiz et al, 2020), echinocandins (Souza et al, 2018), polyenes-particularly amphotericin B (Hernando-Ortiz et al, 2020), and b-lactam antibiotics (in combination with vancomycin) (De Aguiar Cordeiro et al, 2018) have been evaluated for their in vivo efficacy at varying effective concentrations in rescuing worms infected with Candida species (Table 6). Synthesized azole drugs, such as 1-(4cyclopropyl-1H-1,2,3-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl) propan-2-ol, have also been evaluated for both efficacy and cytotoxicity in a C. elegans model (Chen et al, 2017).…”