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Role of filamentation in Galleria mellonella killing by Candida albicans.

ABSTRACT: Candida albicans is an important cause of morbidity in hospitalized and immunosuppressed patients. Virulence factors of C. albicans include: filamentation, proteinases, adherence proteins and biofilm formation. The objective of this work was to use Galleria mellonella as a model to study the roles of C. albicans filamentation in virulence. We focused our study to five genes BCR1, FLO8, KEM1, SUV3 and TEC1 that have been shown to play a role in filamentation. Filaments are necessary for biofilm formation and evading interaction with macrophages in mammalian infections. Among the five mutant strain tested, we found that only the flo8/flo8 mutant strain did not form filaments within G. mellonella. This strain also exhibited reduced virulence in the larvae. Another strain that exhibited reduced pathogenicity in the G. mellonella model was tec1/tec1 but by contrast, the tec1/tec1 strain retained the ability to form filaments. Overexpression of TEC1 in the flo8/flo8 mutant restored filamentation but did not restore virulence in the larvae as well as in a mouse model of C. albicans infection. The filamentation phenotype did not affect the ability of hemocytes, the immune cells of G. mellonella, to associate with the various mutant strains of C. albicans. The capacities of the tec1/tec1 mutant and the flo8/flo8 TDH3-TEC1 strains to form filaments with impaired virulence suggest that filamentation alone is not sufficient to kill G. mellonella and suggest other virulence factors may be associated with genes that regulate filamentation.

SUBMITTER: Fuchs BB

PROVIDER: S-EPMC2883670 | biostudies-other | 2010 Jun

REPOSITORIES: biostudies-other

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Role of filamentation in Galleria mellonella killing by Candida albicans.

Fuchs Beth Burgwyn BB Eby Josh J Nobile Clarissa J CJ El Khoury Joseph B JB Mitchell Aaron P AP Mylonakis Eleftherios E

Microbes and infection 20100309 6

Candida albicans is an important cause of morbidity in hospitalized and immunosuppressed patients. Virulence factors of C. albicans include: filamentation, proteinases, adherence proteins and biofilm formation. The objective of this work was to use Galleria mellonella as a model to study the roles of C. albicans filamentation in virulence. We focused our study to five genes BCR1, FLO8, KEM1, SUV3 and TEC1 that have been shown to play a role in filamentation. Filaments are necessary for biofilm f ...[more]

PMID: 20223293

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Project description:Candidiasis affects a wide variety of immunocompromised and medically compromised patients. Candida albicans, a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non-albicans Candida species (NACS). These species are believed to be less pathogenic, in part, because they do not filament as readily or robustly as C. albicans, although definitive evidence is lacking. To address this question, we used strains for two NACS, Candida tropicalis and Candida parapsilosis, which were genetically engineered to constitutively express the key transcriptional regulator UME6 and drive strong filamentation both in vitro and during infection in vivo Unexpectedly, both strains showed a dramatic reduction in organ fungal burden in response to UME6 expression. Consistent with these findings, we observed that a C. tropicalis hyperfilamentous mutant was significantly reduced and a filamentation-defective mutant was slightly increased for organ fungal burden. Comprehensive immune profiling generally did not reveal any significant changes in the host response to UME6 expression in the NACS that could explain the increased clearance of infection. Interestingly, whole-genome transcriptional profiling indicated that while genes important for filamentation were induced by UME6 expression in C. tropicalis and C. parapsilosis, other genes involved in a variety of processes important for pathogenesis were strongly downregulated. These findings suggest that there are fundamental evolutionary differences in the relationship between morphology and pathogenicity among Candida species and that NACS do not necessarily possess the same virulence properties as C. albicans IMPORTANCE Many immunocompromised individuals, including HIV/AIDS and cancer patients, are susceptible to candidiasis. About half of all cases are caused by the major fungal pathogen Candida albicans, whereas the remainder are due to less pathogenic non-albicans Candida species (NACS). Generation of filamentous cells represents a major virulence property of C. albicans, and the NACS are believed to be less pathogenic, in part, because they do not filament as well as C. albicans does. To address this question, we determined the pathogenicity of two NACS strains that have been genetically engineered to promote filamentation during infection. Surprisingly, these strains showed a dramatic reduction in pathogenicity. The host immune response did not appear to be affected. However, unlike C. albicans, filamentation of the NACS was associated with downregulation of several genes important for pathogenicity processes. Our results suggest that there are fundamental evolutionary differences in the relationship between filamentation and pathogenesis in NACS compared to C. albicans.

Dataset Information

Role of filamentation in Galleria mellonella killing by Candida albicans.

Publications

Role of filamentation in Galleria mellonella killing by Candida albicans.

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