TheGalleria mellonellainfection model as a system to investigate the virulence ofCandida aurisstrains

Abstract

Candida auris is a multiresistant pathogenic yeast commonly isolated from bloodstream infections in immunocompromised patients. In this work, we infected G. mellonella larvae with 105 CFU of a reference strains and two clinical isolates of C. albicans and C. auris and we compared the outcomes of infection between both species. Larvae were evaluated every 24 h for a total of 120 h following the G. mellonella Health Index Scoring System, and survival, activity, melanization and cocoon formation were monitored. Our results showed that clinical isolates were significantly more pathogenic than reference strains independently of the tested species, producing lower survival and activity scores and higher melanization scores, and being C. albicans strains more virulent than C. auris strains. We did not find differences in mortality between aggregative and non-aggregative C. auris strains, although non-aggregative strains produced significantly lower activity scores and higher melanization scores than aggregative ones. Survival assays using Galleria mellonella have been previously employed to examine and classify strains of this and other microbial species based on their virulence before scaling the experiments to a mammal model. Taken together, these results show how a more complete evaluation of the model can improve the study of C. auris isolates.

Pathogenicity Assessment of Colombian Strains of Candida auris in the Galleria mellonella Invertebrate Model

“…Though C. auris virulence is comparable to C. albicans at the concentrations used, Sherry et al showed, at lower concentrations (1 × 10 5 and 5 × 10 4 cells/larvae), some non-aggregating cells are more virulent than C. albicans in G. mellonella [ 31 ]. Our result is in agreement with a study by Romera et al in 2020 where they reported that they did not find differences in larvae mortality induced by aggregated and non-aggregated strains of C. auris [ 32 ].…”

Candida auris: Epidemiology, Diagnosis, Pathogenesis, Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in Healthcare Facilities

“…The ability to aggregate was subsequently shown to be an inducible trait as aggregate formation was stimulated by the prior exposure of C. auris to triazoles or echinocandins [130]. A more recent study has shown that the mortality rates between aggregative and non-aggregative C. auris strains were nearly same; however, clinical isolates were significantly more pathogenic than reference C. auris strains [147]. Aggregative phenotypes of C. auris have predominantly been isolated from colonized patients and have higher capacity for biofilm formation than non-aggregative phenotypes, and these findings are consistent with the difficulties encountered in the eradication of C. auris from most of the colonized patients [70,88].…”

What Do We Know about Candida auris? State of the Art, Knowledge Gaps, and Future Directions

“…Microscopically, C. auris is a yeast with 2–3 × 2.5–5 μm ovoid cells similar to C. glabrata [ 43 ]. It presents two important clearly distinguishable phenotypes with different behaviour and virulence [ 43 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]: Non-aggregative phenotype: yeast cells arrange as isolated or, sometimes, coupled cells, similarly to other Candida species. Aggregative phenotype: some isolates keep daughter cells attached after budding, creating large aggregates that cannot be separated by physical disruption after vigorous vortexing for several minutes.…”

“…Despite C. auris initially being considered unable to filament in vivo or, in any case, only able to produce rudimentary pseudohyphae under stress [ 75 , 76 ], some works using strains from different origins and clones have described an in vivo virulence similar or even greater than that of C. albicans [ 43 , 62 , 97 ]. Nonetheless, the results of the few studies on the pathogenicity of C. auris are relatively diverse, as seen in Table 1 [ 43 , 61 , 62 , 63 , 64 , 65 , 97 ]. Differences have been noted, not only in comparison with other species of the genus, but also regarding different clones, strains, and individual isolates.…”