Candida auris is an emerging multidrug-resistant fungal pathogen responsible for nosocomial outbreaks of invasive candidiasis. Although several studies on the pathogenicity of this species have been reported, the knowledge on C. auris virulence is still limited. This study aims to analyze the pathogenicity of C. auris , using one aggregating isolate and eleven non-aggregating isolates from different clinical origins (blood, urine and oropharyngeal specimens) in two alternative host models of candidiasis: Caenorhabditis elegans and Galleria mellonella . Furthermore, possible associations between virulence, aggregation, biofilm-forming capacity, and clinical origin were assessed. The aggregating phenotype isolate was less virulent in both in vivo invertebrate infection models than non-aggregating isolates but showed higher capacity to form biofilms. Blood isolates were significantly more virulent than those isolated from urine and respiratory specimens in the G. mellonella model of candidiasis. We conclude that both models of candidiasis present pros and cons but prove useful to evaluate the virulence of C. auris in vivo . Both models also evidence the heterogeneity in virulence that this species can develop, which may be influenced by the aggregative phenotype and clinical origin.

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.

Candida albicans is the major etiological agent of invasive candidiasis but the increasing prevalence of emerging species of Candida, such as Candida glabrata and phylogenetically closely related species, Candida nivariensis and Candida bracarensis, requires special attention. Differences in virulence among these species and their therapeutic responses using in vivo non-mammalian models are scarcely analysed. The aim of this study was analyse the survival of G. mellonella and host-pathogen interactions during infection by C. glabrata, C. nivariensis and C. bracarensis. Moreover, therapeutic responses to echinocandins were also assessed in the G. mellonella model of candidiasis. These three species produced lethal infection in G. mellonella; C. glabrata was the most virulent species and C. bracarensis the less. Haemocytes of G. mellonella phagocytised C. bracarensis cells more effectively than those of the other two species. Treatment with caspofungin and micafungin was most effective to protect larvae during C. glabrata and C. nivariensis infections while anidulafungin was during C. bracarensis infection. The model of candidiasis in G. mellonella is simple and appropriate to assess the virulence and therapeutic response of these emerging Candida species. Moreover, it successfully allows for detecting differences in the immune system of the host depending on the virulence of pathogens.

Kandidiasia Candida generoko espezieek eragindako infekzio mikotikoa da. Candida albicans agente etiologiko nagusia da baina gero eta gehiagotan Candida generoko beste espezie batzuk agertzen ari dira kandidiasiaren eragile bezala eta, hauen artean, Candida glabrata espeziea. Espezie honekin lotuta beste bi espezie daude, Candida bracarensis eta Candida nivariensis, teknika molekularrek ondo desberdindu ditzaketenak. Aldaketa etiologiko hauek ondorio larriak izan ditzakete kandidiasiaren diagnostikoan, tratamenduan edota pronostikoan, besteak beste, bere patogenia edo antifungikoekiko sentikortasuna oso desberdina izan daitezkeelako. Ordezko eredu esperimentalek erabiliz mikroorganismoek eragindako gaixotasunen patogenia eta terapia ezagutzeko ezinbesteko aukera ematen dizkigute, eta hauen artean, Caenorhabditis elegans nematodoa eta Galleria mellonella lepidopteroa ditugu. Ikerketa lan honetan konbentzionalak ez diren bi animalia eredu hauen erabilgarritasuna ebaluatu nahi izan da Candida glabrata, Candida bracarensis eta Candida nivariensis harreman filogenetiko estua duten hiru espezie hauen birulentzia in vivo aztertzeko.