Pathogenicity Levels of Colombian Strains of Candida auris and Brazilian Strains of Candida haemulonii Species Complex in Both Murine and Galleria mellonella Experimental Models

Abstract

<jats:p>Candida auris and Candida haemulonii complex (C. haemulonii, C. haemulonii var. vulnera and C. duobushaemulonii) are phylogenetically related species that share some physiological features and habits. In the present study, we compared the virulence of these yeast species using two different experimental models: (i) Galleria mellonella larvae to evaluate the survival rate, fungal burden, histopathology and phagocytosis index and (ii) BALB/c mice to evaluate the survival. In addition, the fungal capacity to form biofilm over an inert surface was analyzed. Our results showed that in both experimental models, the animal survival rate was lower when infected with C. auris strains than the C. haemulonii species complex. The hemocytes of G. mellonella showed a significantly reduced ability to phagocytize the most virulent strains forming the C. haemulonii species complex. Interestingly, for C. auris, it was impossible to measure the phagocytosis index due to a general lysis of the hemocytes. Moreover, it was observed a greater capability of biofilm formation by C. auris compared to C. haemulonii species complex. In conclusion, we observed that C. auris and C. haemulonii complex have different levels of pathogenicity in the experimental models employed in the present study.</jats:p>

Virulence ofCandida aurisfrom different clinical origins inCaenorhabditis elegansandGalleria mellonellahost models

“…These results are consistent with those reported by Borman et al (2016) [ 21 ] who first described the formation of aggregates by some C. auris isolates, which later was corroborated by Sherry et al (2017) [ 22 ] and Muñoz et al (2020) [ 11 ]. These studies reported that C. auris did not form hyphae unlike C. albicans in the G. mellonella model of candidiasis, and that non-aggregating C. auris isolates were more virulent, even when compared to some C. albicans isolates [ 11 , 21 , 22 ]. In a murine model, Ben-Ami et al (2017) [ 13 ] also identified yeast cells during the infection and recovered aggregates from murine tissues.…”

“…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 ].…”

“…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 ]. However, also within the species C. auris differences in virulence between isolates from different clades have been noted, probably associated with their genomic diversity [ 12 ].…”

“…However, ethical and economical issues for using these models of candidiasis are encouraging the use of alternative systems such as invertebrate models [ 19 , 20 ]. Several virulence studies of C. auris infections have been reported in invertebrate models using Caenorhabditis elegans, Drosophila melanogaster, Danio rerio or Galleria mellonella [ 11 , 21–29 ]. Moreover, non-mammalian hosts have been successfully implemented for studying host-pathogen interactions and invasive candidiasis caused by other Candida species, and to evaluate the effectiveness of new therapeutic approaches [ 11 , 30–33 ].…”

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

“…For this reason, different models that are easier to use have recently been chosen, and one of them is the invertebrate Galleria mellonella . In recent years, this experimental model has been crucial for understanding the pathogenicity of different Candida species, and relatively inexpensive compared to the murine model [ 16 , 17 ]. The advantage of using G. mellonella as a model for the study of pathogenicity in fungi is the ease of use, that is, the inoculation of the pathogen involves only a hind leg and a syringe, and they can be maintained at variable temperatures ranging from 25 to 37 °C.…”