Phenotypic switching in Candida tropicalis alters host-pathogen interactions in a Galleria mellonella infection model

Hugo F Perini,Admilton O G Junior,Fernando Gomes Barcellos,Marcia C Furlaneto,Ricardo S C Almeida,Luciana Furlaneto-Maia,Alane T P Moralez,Luciano A Panagio

doi:10.1038/s41598-019-49080-6

Abstract

Candida tropicalis is a human pathogen associated with high mortality rates. We have reported a switching system in C. tropicalis consisting of five morphotypes – the parental, switch variant (crepe and rough), and revertant (crepe and rough) strains, which exhibited altered virulence in a Galleria mellonella model. Here, we evaluate whether switching events may alter host-pathogen interactions by comparing the attributes of the innate responses to the various states. All switched strains induced higher melanization in G. mellonella larvae than that induced by the parental strain. The galiomicin expression was higher in the larvae infected with the crepe and rough morphotypes than that in the larvae infected with the parental strain. Hemocytes preferentially phagocytosed crepe variant cells over parental cells in vitro. In contrast, the rough variant cells were less phagocytosed than the parental strain. The hemocyte density was decreased in the larvae infected with the crepe variant compared to that in the larvae infected with the parental strain. Interestingly, larvae infected with the revertant of crepe restored the hemocyte density levels that to those observed for larvae infected with the parental strain. Most of the switched strains were more resistant to hemocyte candidacidal activity than the parental strain. These results indicate that the switch states exhibit similarities as well as important differences during infection in a G. mellonella model.

Highlights

Phenotypic switching is a strategy that allows microorganisms to undergo adaptation to environmental changes
We aimed to evaluate the influence of phenotypic switching on larval humoral defense, the production of melanin, which is a key step in the antimicrobial response of G. mellonella
The revertant of crepe (CR) and the revertant of rough (RR) induced higher melanization than the parental strain (Fig. 2B), despite their parental-like colony morphology. These data suggest that phenotypic switching in C. tropicalis generates strains that are differently recognized by G. mellonella larvae

Summary

Introduction

Phenotypic switching is a strategy that allows microorganisms to undergo adaptation to environmental changes. Similar to C. albicans, C. tropicalis makes use of a tristable switching system between the white, gray, and opaque cell types[11]. C. tropicalis gray cells exhibit an intermediate level of mating capability and virulence in a mouse infection model compared to that of white and opaque cell types[11]. Larvae of the greater wax moth G. mellonella are a well-accepted model for the study of fungal pathogen-host interactions and serve as complementary hosts to conventional vertebrate animal models[15,16]. This invertebrate model exhibits several traits that make it a useful model for fungal pathogenesis studies. The cellular immune response is mediated by phagocytic cells, termed hemocytes[19], while the humoral defenses involve the production of effector molecules such as melanin and antimicrobial peptides[20]

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Conclusion