Characterization of Virulence Properties in the C. parapsilosis Sensu Lato Species

Abstract

The C. parapsilosis sensu lato group involves three closely related species, C. parapsilosis sensu stricto, C . orthopsilosis and C . metapsilosis . Although their overall clinical importance is dramatically increasing, there are few studies regarding the virulence properties of the species of the psilosis complex. In this study, we tested 63 C. parapsilosis sensu stricto, 12 C . metapsilosis and 18 C . orthopsilosis isolates for the ability to produce extracellular proteases, secrete lipases and form pseudohyphae. Significant differences were noted between species, with the C . metapsilosis strains failing to secrete lipase or to produce pseudohyphae. Nine different clinical isolates each of C. parapsilosis sensu stricto, C . orthopsilosis and C . metapsilosis were co-cultured with immortalized murine or primary human macrophages. C. parapsilosis sensu stricto isolates showed a significantly higher resistance to killing by primary human macrophages compared to C . orthopsilosis and C . metapsilosis isolates. In contrast, the killing of isolates by J774.2 mouse macrophages did not differ significantly between species. However, C. parapsilosis sensu stricto isolates induced the most damage to murine and human macrophages, and C . metapsilosis strains were the least toxic. Furthermore, strains that produced lipase or pseudohyphae were most resistant to macrophage-mediated killing and produced the most cellular damage. Finally, we used 9 isolates of each of the C. parapsilosis sensus lato species to examine their impact on the survival of Galleria mellonella larvae. The mortality rate of G . mellonella larvae infected with C . metapsilosis isolates was significantly lower than those infected with C. parapsilosis sensu stricto or C . orthopsilosis strains. Taken together, our findings demonstrate that C . metapsilosis is indeed the least virulent member of the psilosis group, and also highlight the importance of pseudohyphae and secreted lipases during fungal-host interactions.

Species Distribution, Virulence Factors, and Antifungal Susceptibility Among Candida parapsilosis Complex Isolates Recovered from Clinical Specimens

“…Indeed, it is widely accepted that aging is associated with a decline in immune function, a process termed immune senescence, which makes an individual more susceptible to infections [36], including opportunistic fungal infections [37]. The assumption that aging is a risk factor for infection with C. metapsilosis could be in line with previous work showing that this yeast is the least virulent species of the group [34,38]. However, to date there are few reports with information about patients' age, and thus, further studies with a greater number of isolates and extensive demographic information are needed to confirm the association between aging and infection by C. metapsilosis.…”

Characterization of Virulence-Related Phenotypes in Candida Species of the CUG Clade

“…Although intraspecies strain variation can be significant (see, for instance, references 50, 51, 52, and 53), several additional C. parapsilosis species fared no better than did CDC317, the sequenced reference isolate used in most of our studies. Another recent study that looked at a larger set of C. parapsilosis clinical isolates also concluded that, while there were phenotypic differences in vitro, the effects on host interactions were modest (54). The discrepancy between the lab and the clinic might be explained if C. parapsilosis were more common as a commensal or more easily transmitted from person to person, such that patients were exposed to it more frequently.…”

The Candida Pathogenic Species Complex

“…Close relatives include C. orthopsilosis and C. metapsilosis, once characterized as belonging to the same species (Tavanti et al 2005). C. orthopsilosis and C. metapsilosis are much less frequent causes of infection than C. parapsilosis (Table 1) and are less virulent in animal models (Nemeth et al 2013). Comparing the genomes of C. parapsilosis and C. orthopsilosis suggests that amplification of gene families, in particular of cell wall genes, is associated with increased virulence of C. parapsilosis (Riccombeni et al 2012).…”