Characterization of Biofilm Formation and the Role of BCR1 in Clinical Isolates of Candida parapsilosis

Abstract

eIn Candida parapsilosis, biofilm formation is considered to be a major virulence factor. Previously, we determined the ability of 33 clinical isolates causing bloodstream infection to form biofilms and identified three distinct groups of biofilm-forming strains (negative, low, and high). Here, we establish two different biofilm structures among strains forming large amounts of biofilm in which strains with complex spider-like structures formed robust biofilms on different surface materials with increased resistance to fluconazole. Surprisingly, the transcription factor Bcr1, required for biofilm formation in Candida albicans and C. parapsilosis, has an essential role only in strains with low capacity for biofilm formation. Although BCR1 leads to the formation of more and longer pseudohyphae, it was not required for initial adhesion and formation of mature biofilms in strains with a high level of biofilm formation. Furthermore, an additional phenotype affected by BCR1 was the switch in colony morphology from rough to crepe, but only in strains forming high levels of biofilm. All bcr1⌬/⌬ mutants showed increased proteolytic activity and increased susceptibility to the antimicrobial peptides protamine and RP-1 compared to corresponding wild-type and complemented strains. Taken together, our results demonstrate that biofilm formation in clinical isolates of C. parapsilosis is both dependent and independent of BCR1, but even in strains which showed a BCR1-independent biofilm phenotype, BCR1 has alternative physiological functions.

The Oral Cavity: A Reservoir that Favors Colonization and Selection of Candida parapsilosis sensu stricto Strains with High Pathogen Potential Under Conditions of Gingival-periodontal Disease

“…This fact has already been demonstrated in several studies; it has also been reported that biofilm formation by Candida parapsilosis is a key virulence factor in this species, highly dependent on the strain [51,52], an unproven characteristic in other NAC species such as C. glabrata and C. tropicalis [51]. In our case, from all the clinical C. parapsilosis sensu stricto isolates sorted according to biofilm biomass, concurrent results with those from Silva et al [48] and Pannanusorn et al [52] were found, since we identified strains with different biofilm-forming capacity (high, low and nonexistent), where high biofilm-forming capacity strains predominated in both RPMI and YPD media (71 % and 79 %, respectively). This result also agrees with the findings from Silva et al, given that in the clinical C. parapsilosis sensu stricto isolates analyzed by them regarding biofilm-forming capacity, oral isolates were found to be the most common biofilm producers with respect to strains from vaginal and urinary tracts.…”

Candida Biofilms: Development, Architecture, and Resistance

“…Proteomics analysis of biofilm matrix isolated using this optimized method revealed the presence of specific proteins (including glyceraldehyde 3-phosphate dehydrogenase and pyruvate kinase) in the biofilm matrix. Additional Candida genes implicated in biofilm formation include ACE2 ( 93 ), YWP1 ( 94 ), HWP1 ( 95 ), LL34 ( RIX7 ) ( 96 ), ALS3 ( 97 , 98 ), GAL10 ( 99 ), VPS1 ( 100 ), SUR7 ( 101 ), GUP1 ( 102 ), PEP12 ( 103 ), TPK1/2 ( 104 ), NRG1 (transcriptional repressor) and its target BRG1 (GATA family transcription factor) ( 105 ), UME6 (transcriptional regulator), HGC1 (a cyclin-related protein), SUN41 (a putative cell wall glycosidase), EFG1 ( 106 , 107 ), STV1 and VPH1 (Golgi/vacuolar subunits of vacuolar proton-translocating ATPase isoforms) ( 108 ), CEK1 (map kinase) ( 109 ), CDK8 ( 88 ), BCR1 ( 110 ), SPT20 ( 111 ), and SAC1 (PIP phosphatase) ( 112 ). In addition, quorum sensing molecules (such as 3R-hydroxy-tetradecaenoic acid [3R-HTDE, a beta-oxidation metabolite of endogenously present linoleic acid] [ 113 ]), farnesol ( 114 – 117 ), and cis -2-dodecenoic acid (BDSF) ( 118 ) and metabolic processes (e.g., carbohydrate assimilation, amino acid metabolism, and intracellular transport) ( 119 ) and glycolytic flux and hypoxia adaptation ( 120 ) have been suggested to play critical roles in Candida biofilm formation.…”

Production of protein and metabolites by yeast grown in solid state fermentation: present status and perspectives

“…Biofilms are defined as microbial communities encased in a matrix of extracellular polymeric substances . The composition and regulation analysis of gene expression for the constitution of biofilms comes mainly from studies on pathogenic yeast such as Candida sp . However, there are also studies that have focused on other yeasts with biotechnological interest such as S. cerevisiae .…”