Genetic Control of Conventional and Pheromone-Stimulated Biofilm Formation in Candida albicans

Ching-Hsuan Lin,Shail Kabrawala,Emily P Fox,Clarissa J Nobile,Richard J Bennett,Alexander D Johnson,Alistair J P Brown

doi:10.1371/journal.ppat.1003305

Abstract

Candida albicans can stochastically switch between two phenotypes, white and opaque. Opaque cells are the sexually competent form of C. albicans and therefore undergo efficient polarized growth and mating in the presence of pheromone. In contrast, white cells cannot mate, but are induced – under a specialized set of conditions – to form biofilms in response to pheromone. In this work, we compare the genetic regulation of such “pheromone-stimulated” biofilms with that of “conventional” C. albicans biofilms. In particular, we examined a network of six transcriptional regulators (Bcr1, Brg1, Efg1, Tec1, Ndt80, and Rob1) that mediate conventional biofilm formation for their potential roles in pheromone-stimulated biofilm formation. We show that four of the six transcription factors (Bcr1, Brg1, Rob1, and Tec1) promote formation of both conventional and pheromone-stimulated biofilms, indicating they play general roles in cell cohesion and biofilm development. In addition, we identify the master transcriptional regulator of pheromone-stimulated biofilms as C. albicans Cph1, ortholog of Saccharomyces cerevisiae Ste12. Cph1 regulates mating in C. albicans opaque cells, and here we show that Cph1 is also essential for pheromone-stimulated biofilm formation in white cells. In contrast, Cph1 is dispensable for the formation of conventional biofilms. The regulation of pheromone- stimulated biofilm formation was further investigated by transcriptional profiling and genetic analyses. These studies identified 196 genes that are induced by pheromone signaling during biofilm formation. One of these genes, HGC1, is shown to be required for both conventional and pheromone-stimulated biofilm formation. Taken together, these observations compare and contrast the regulation of conventional and pheromone-stimulated biofilm formation in C. albicans, and demonstrate that Cph1 is required for the latter, but not the former.

Highlights

Candida albicans is a prevalent pathogen of humans that colonizes and infects multiple niches in the mammalian host
We compare the regulation of biofilm formation in conventional biofilms, for which a core transcriptional network has recently been identified, with pheromone-stimulated biofilms, which occur when C. albicans white cells are exposed to pheromone
Our studies show that several regulatory components control biofilm formation under both conditions, including the network transcriptional regulators Bcr1, Brg1, Rob1, and Tec1

Summary

Introduction

Candida albicans is a prevalent pathogen of humans that colonizes and infects multiple niches in the mammalian host. To achieve such extreme adaptability, this pathogen has evolved genetic and epigenetic mechanisms that modulate cell behavior and morphology in response to environmental signals. Epigenetic variation in C. albicans is perhaps best exemplified by the white-opaque phenotypic switch. This is a heritable and reversible switch in which cells transition between white cells that are round and give rise to dome-shaped, shiny colonies, and opaque cells that are elongated and give rise to flatter, darker colonies [1]. Switching is regulated by a core circuit of transcription factors that operate within a network of positive and negative feedback loops [2,3]. Similar transcriptional networks are found in many biological systems and act to regulate developmental programs from yeast to mammals [3,4]

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