Phenotypic switching inCandida tropicalis: association with modification of putative virulence attributes and antifungal drug sensitivity

Abstract

Although Candida tropicalis has become an increasingly important human pathogen, little is known regarding its potential to cause disease. In this study we evaluated the phenotypic switching ability of C. tropicalis and analyzed the effect of switching on biological properties related to virulence factors. We demonstrated that C. tropicalis switched spontaneously, reversibly and at high frequency (10(-1) to 10(-3)) when grown on yeast extract-peptone-D-glucose (YPD) agar medium. Phenotypic switching in five clinical isolates of C. tropicalis resulted in colonies exhibiting the following morphologies: crepe, rough, crater, irregular center, mycelial and diffuse. The majority of the variant colonies were associated with higher percentages of filamentous growth relative to their parental unswitched isolates. Significant differences (P < 0.05) in the production of hemolytic factor were found between most of the switched variants and their respective parental counterparts. Variant colonies exhibiting the crepe (derived from isolates 49.07 and 100.10) and rough phenotype (derived from isolate 49.07) had higher biofilm formation than their parental counterparts exhibiting a smooth dome surface (P < 0.05). Our data revealed that switching was correlated with changes in the in vitro minimum inhibitory concentrations (MICs) of a subset of the switched variants phenotypes to itraconazole. While the MIC to itraconazole was higher for crepe variant compared with its parental isolate 49.07, the rough variant of 100.10 had a lower MIC to this antifungal agent. The presented data support the role of phenotypic switching in promoting changes in phenotypic expression of putative virulence traits and itraconazole susceptibility of clinical isolates of C. tropicalis.

Phenotypic switching ofCandida tropicalisis associated with cell damage in epithelial cells and virulence inGalleria mellonellamodel

“…These data may reflect differential expression of virulence traits by this switched strain. In previous study, 5 we reported that the crepe variant colonies had increased percentage of filamentous growth forms; besides, the crepe variant formed higher amount of biofilm and increased MIC to the antifungal itraconazole compared to that observed for its unswitched parental (original smooth). These altered traits could potentially affect virulence.…”

“…4,5 The isolates could switch spontaneously, heritably and reversibly between at least six different phenotypes, not including the white-opaque transition. 4,5 One of the identified switching system that include three colony phenotypes: smooth (parental phenotype) and two related switch variants (crepe and rough) was associated with in vitro changes in virulence traits, including biofilm formation, morphogenesis and hemolysis, as well as switching from itraconazole susceptibility to resistance. 5 Soll et al 6 were the first to assess switch phenotypes in C. tropicalis during the course of a prolonged Candida infection in a compromised host.…”

“…4,5 One of the identified switching system that include three colony phenotypes: smooth (parental phenotype) and two related switch variants (crepe and rough) was associated with in vitro changes in virulence traits, including biofilm formation, morphogenesis and hemolysis, as well as switching from itraconazole susceptibility to resistance. 5 Soll et al 6 were the first to assess switch phenotypes in C. tropicalis during the course of a prolonged Candida infection in a compromised host. Further, a white-opaque phenotypic switch was described for C. tropicalis that shows some similarities to that in Candida albicans.…”

“…14,15 In the present study, we address for the first time in the literature, if phenotypic switching affects virulence in C. tropicalis. To this end, we employed all three colony phenotypes (smooth, crepe and rough) described previously 5 and revertants (strains that switched back from variant to parental phenotype) for the evaluation of the capacity of damaging epithelial cells and virulence in Galleria mellonella. The switched strains (crepe and rough variants) were obtained as individual subclones from a clinical isolate exhibiting a smooth colony dome.…”

Candida tropicalis bloodstream infection: Incidence, risk factors and outcome in a population-based surveillance

“…3,4 As compared to other species, C. tropicalis depicts various distinct features that increase its intrinsic pathogenicity, 5 including its capability for secretion of extracellular hydrolytic enzymes (coagulase, phospholipase or proteinase), 6,7 biofilm formation 7 and phenotypic switching. 8 In addition, clinical studies have suggested a particular susceptibility to C. tropicalis BSI among neutropenic patients with haematological and solid-organ malignancies. 9e11 Therefore, the outcome of this form of invasive fungal disease is generally assumed to be poorer in comparison to that of BSI due to other Candida species.…”