Invasive candidiasis is caused mainly by Candida albicans, but other Candida species have increasing etiologies. These species show different virulence and susceptibility levels to antifungal drugs. The aims of this study were to evaluate the usefulness of the non-conventional model Caenorhabditis elegans to assess the in vivo virulence of seven different Candida species and to compare the virulence in vivo with the in vitro production of proteinases and phospholipases, hemolytic activity and biofilm development capacity. One culture collection strain of each of seven Candida species (C. albicans, Candida dubliniensis, Candida glabrata, Candida krusei, Candida metapsilosis, Candida orthopsilosis and Candida parapsilosis) was studied. A double mutant C. elegans AU37 strain (glp-4;sek-1) was infected with Candida by ingestion, and the analysis of nematode survival was performed in liquid medium every 24 h until 120 h. Candida establishes a persistent lethal infection in the C. elegans intestinal tract. C. albicans and C. krusei were the most pathogenic species, whereas C. dubliniensis infection showed the lowest mortality. C. albicans was the only species with phospholipase activity, was the greatest producer of aspartyl proteinase and had a higher hemolytic activity. C. albicans and C. krusei caused higher mortality than the rest of the Candida species studied in the C. elegans model of candidiasis.
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.
Los autores declaran no tener conflicto de interés respecto a la presente investigación. Este estudio no tuvo financiamiento, la empresa Galénica aportó los reactivos, pero no tuvo ninguna influencia ni en el diseño ni en el análisis de los resultados o su publicación.
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.
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