The role of Candida albicans SPT20 in filamentation, biofilm formation and pathogenesis.

Xiaojiang Tan,Rosalyn B Chen,Beth Burgwyn Fuchs,Cleo Anastassopoulou,Eleftherios Mylonakis,Jeffrey J Coleman,Yan Wang,Read Pukkila-Worley,Weiping Chen,Elamparithi Jayamani,Grace J Yuen

doi:10.1371/journal.pone.0094468

Abstract

Candida albicans is a ubiquitous fungus, which can cause very serious and sometimes life-threatening infections in susceptible patients. We used Caenorhabditis elegans as a model host to screen a library of C. albicans mutants for decreased virulence and identified SPT20 as important for virulence. The transcription co-activator SPT20 was identified originally as a suppressor of Ty and solo δ insertion mutations, which can cause transcription defects in Saccharomyces cerevisiae. It is resistant to the toxicity caused by overexpression of GAL4-VP16. We constructed a C. albicans spt20Δ/Δ mutant and found the spt20Δ/Δ strain was significantly less virulent than the wild-type strain SC5314 in C. elegans (p < 0.0001), Galleria mellonella (p < 0.01) and mice (p < 0.001). Morphologically, spt20Δ/Δ mutant cells demonstrated a “snow-flake” shape and clustered together; prolonged culture times resulted in increased size of the cluster. The clustered morphology was associated with defects in nuclei distribution, as the nuclei were not observed in many cellular compartments. In addition, the C. albicans spt20Δ/Δ mutant resulted in defects in hyphae and biofilm formation (compared to the wild-type strain, p < 0.05), and sensitivity to cell wall and osmotic stressors, and to antifungal agents. Thus our study demonstrated a role of C. albicans SPT20 in overall morphology and distribution of nuclear material, which may cause the defects in filamentation and biofilm formation directly when this gene is deleted.

Highlights

Candida albicans is part of the human flora that can be isolated from the gastrointestinal tract, vagina, and mouth in healthy individuals
We show that in C. albicans, SPT20 plays a role in maintaining cell wall integrity
The defects in the cell wall are coupled with altered morphology and the inability of spt20D/D cells to form hyphae and generate a biofilm

Summary

Introduction

Candida albicans is part of the human flora that can be isolated from the gastrointestinal tract, vagina, and mouth in healthy individuals. C. albicans is the fourth most common pathogen isolated from blood cultures and candidemia is associated with mortality rates as high as 35% [2] or even higher [3,4]. A characteristic of C. albicans is that it can make the switch between several morphological forms: budding yeast, pseudohyphae, and true hyphae, according to the environmental conditions [5,6]. The pathogenic ability of C. albicans is closely related to the change between these morphological forms [7,8]. The formation of hyphae [9] and biofilms [10], the integrity of the cell wall [11], the rapid adaptive capacity to external environmental condition [12] all contribute to virulence and are all related to morphogenesis

Methods

Results

Conclusion