Temporal analysis of Candida albicans gene expression during biofilm development

Abstract

Microarrays were used to identify changes in gene expression associated with Candida albicans biofilm development. Two biofilm substrates (denture and catheter), and two C. albicans strains for each substrate, were tested to remove model-and strain-dependent variability from the overall dataset. Three biofilm developmental phases were examined: early (6 h), intermediate (12 h), and mature (48 h). Planktonic specimens were collected at the same time points. Data analysis focused primarily on gene expression changes over the time-course of biofilm development. Glycolytic and non-glycolytic carbohydrate assimilation, amino acid metabolism, and intracellular transport mechanisms were important during the early phase of biofilm formation. These early events increase intracellular pools of pyruvate, pentoses and amino acids, which prepare the biofilm for the large biomass increase that begins around 12 h of development. This developmental stage demands energy and utilizes specific transporters for amino acids, sugars, ions, oligopeptides and lactate/pyruvate. At mature phase (48 h), few genes were differentially expressed compared with the 12 h time point, suggesting a relative lack of initiation of new metabolic activity. Data analysis to assess biofilm model-specific gene expression showed more dynamic changes in the denture model than in the catheter model. Data analysis to identify gene expression changes that are associated with each strain/substrate combination identified the same types of genes that were identified in the analysis of the entire dataset. Collectively, these data suggest that genes belonging to different, but interconnected, functional categories regulate the morphology and phenotype of C. albicans biofilm. INTRODUCTIONMicro-organisms attach to surfaces in many natural, industrial and medical environments and can develop into biofilms. Biofilms are a functional association of microbial cells that are enveloped within extracellular polymer matrices and associated with surfaces (Costerton et al., 1987;Donlan, 2002;Donlan & Costerton, 2002). Phenotypically, biofilm cells are different from planktonic (free-floating) cells (Costerton et al., 1995), with one of the most important manifestations of these differences being the significantly decreased susceptibility of microbial biofilms to antimicrobial agents (Rupp, 2005;Schwank et al., 1998;Stewart et al., 2004;Wilson, 1996). Although bacterial biofilms have been the focus of many studies, detailed investigations into the biology and pathogenesis of fungal biofilms have only recently been initiated (reviewed by Douglas, 2003;Ghannoum & O'Toole, 2004). Candida albicans is the most common fungal pathogen associated with colonization and biofilm formation on the surfaces of indwelling medical devices (IMDs) such as dentures and intravenous catheters (Kojic & Darouiche, 2004). Biofilm formation by C. albicans can promote superficial or systemic disease. For example, denture stomatitis, a superficial candidiasis, occurs in 65 % of denture-wearing Abbrevi...

Susceptibility To Caspofungin And Fluconazole And Als1/Als3 Gene Expression In Biofilm And Dispersal Cells Of Candida Albicans / Profil Osjetljivosti Na Kaspofungin I Flukonazol I Ekspresija Gena Als1 I Als3 U Stanicama Biofilma Te Planktonskim Stanicama Vrste Candida Albicans

“…To date, only a few genes participating in dispersion have been profi led (15,32). Our study has provided new data on the expression of two important genes encoding for adhesins Als1 and Als3, completing the earlier fi ndings (11,16,19). In agreement with them the Als1 gene was signifi cantly up-regulated in the early biofi lm stage, and the Als3 gene in the mature one.…”

“…C. albicans adhesins Als1 and Als3 play an important role and are highly expressed in in vitro (16) as well as in vivo biofi lms (17,18). While the Als1 gene is expressed in the earlier stages of biofi lm formation (19), the Als3 gene is mainly up-regulated in the mature biofi lm (11). However, this is not a rule, as the expression of either gene can be signifi cantly affected by cultivation conditions (11,20).…”

Detailed comparison of Candida albicans and Candida glabrata biofilms under different conditions and their susceptibility to caspofungin and anidulafungin

“…Yeater et al (2007) demonstrated, by microarray analyses of biofilms, that the expression of ALS1 increases during the early stages of biofilm development (6-12 h) and declines at the later stages. This documented profile of expression could explain why we did not observe any regulation of ALS1 under any of the conditions tested, as biofilms were grown for 48 h before analyses.…”

The Activity of Fungichromin against the Formation of <i>Candida albicans</i> Biofilm

“…33) ALS gene family, the member encoding cell-wall glycoproteins, is an important factor for the adhesion of C. albicans. 34,35) It has been reported that ALS1 gene is expressed in the earlier stage of biofilm formation, 36) and ALS3 gene is mainly up-regulated in the mature biofilm. 37) HWP1 gene could also regulate the adhesion of C. albicans to epithelial cells by Hwp1 protein.…”