Conserved and Divergent Roles of Bcr1 and CFEM Proteins in Candida parapsilosis and Candida albicans

Chen Ding,Geraldine Butler,David R Andes,Genevieve M Vidanes,John M Synnott,Sarah L Maguire,Alessandro Guida,Robert Alan Arkowitz

doi:10.1371/journal.pone.0028151

Chen Ding, Geraldine Butler + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0028151

Copy DOI

Abstract

Candida parapsilosis is a pathogenic fungus that is major cause of hospital-acquired infection, predominantly due to growth as biofilms on indwelling medical devices. It is related to Candida albicans, which remains the most common cause of candidiasis disease in humans. The transcription factor Bcr1 is an important regulator of biofilm formation in vitro in both C. parapsilosis and C. albicans. We show here that C. parapsilosis Bcr1 is required for in vivo biofilm development in a rat catheter model, like C. albicans. By comparing the transcription profiles of a bcr1 deletion in both species we found that regulation of expression of the CFEM family is conserved. In C. albicans, three of the five CFEM cell wall proteins (Rbt5, Pga7 and Csa1) are associated with both biofilm formation and acquisition of iron from heme, which is an important virulence characteristic. In C. parapsilosis, the CFEM family has undergone an expansion to 7 members. Expression of three genes (CFEM2, CFEM3, and CFEM6) is dependent on Bcr1, and is induced in low iron conditions. All three are involved in the acquisition of iron from heme. However, deletion of the three CFEM genes has no effect on biofilm formation in C. parapsilosis. Our data suggest that the role of the CFEM family in iron acquisition is conserved between C. albicans and C. parapsilosis, but their role in biofilm formation is not.

Highlights

Candida species are among the most common causes of nosocomial bloodstream infection, and have associated mortality rates ranging from 28–59% [1,2]
Our analysis shows that the Bcr1 transcription factor is an important regulator of biofilm development in vitro and in vivo in the two species, and that regulation of expression of some members of the CFEM family is conserved [16,17,18]
The Bcr1-dependent CFEM genes do not play a role in biofilm development in C. parapsilosis

Summary

Introduction

Candida species are among the most common causes of nosocomial bloodstream infection, and have associated mortality rates ranging from 28–59% [1,2]. Often found as commensal organisms with humans, Candida species are capable of growth as antifungal-resistant biofilms on non-biological surfaces such as medical equipment. Whereas all Candida species form biofilms on solid surfaces, the structures are highly variable [10,11]. In C. albicans, biofilms are multilayered and contain yeast cells, pseudohyphae and hyphae [12]. Adherence of yeast cells to the substrate is followed by an intermediate stage where hyphae are formed and an extracellular matrix is generated. A mature biofilm consists of densely packed hyphae and yeast cells surrounded by the extracellular matrix, consisting mostly of polysaccharides [14]. C. parapsilosis biofilms in contrast consist of a dense network of yeast cells and pseudohyphae, but they contain large amounts of carbohydrate [11,15]

Methods

Results

Conclusion