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PMID:16839200

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Citation

Nobile, CJ, Andes, DR, Nett, JE, Smith, FJ, Yue, F, Phan, QT, Edwards, JE, Filler, SG and Mitchell, AP (2006) Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog. 2:e63

Abstract

The fungal pathogen Candida albicans is frequently associated with catheter-based infections because of its ability to form resilient biofilms. Prior studies have shown that the transcription factor Bcr1 governs biofilm formation in an in vitro catheter model. However, the mechanistic role of the Bcr1 pathway and its relationship to biofilm formation in vivo are unknown. Our studies of biofilm formation in vitro indicate that the surface protein Als3, a known adhesin, is a key target under Bcr1 control. We show that an als3/als3 mutant is biofilm-defective in vitro, and that ALS3 overexpression rescues the biofilm defect of the bcr1/bcr1 mutant. We extend these findings with an in vivo venous catheter model. The bcr1/bcr1 mutant is unable to populate the catheter surface, though its virulence suggests that it has no growth defect in vivo. ALS3 overexpression rescues the bcr1/bcr1 biofilm defect in vivo, thus arguing that Als3 is a pivotal Bcr1 target in this setting. Surprisingly, the als3/als3 mutant forms a biofilm in vivo, and we suggest that additional Bcr1 targets compensate for the Als3 defect in vivo. Indeed, overexpression of Bcr1 targets ALS1, ECE1, and HWP1 partially restores biofilm formation in a bcr1/bcr1 mutant background in vitro, though these genes are not required for biofilm formation in vitro. Our findings demonstrate that the Bcr1 pathway functions in vivo to promote biofilm formation, and that Als3-mediated adherence is a fundamental property under Bcr1 control. Known adhesins Als1 and Hwp1 also contribute to biofilm formation, as does the novel protein Ece1.

Links

PubMed PMC1487173 Online version:10.1371/journal.ppat.0020063

Keywords

Animals; Biofilms/growth & development; Candida albicans/genetics; Candida albicans/pathogenicity; Candida albicans/physiology; Candidiasis/etiology; Candidiasis/genetics; Candidiasis/physiopathology; Catheterization/adverse effects; Cell Adhesion/genetics; Cell Adhesion/physiology; Cell Adhesion Molecules/physiology; Fungal Proteins/genetics; Fungal Proteins/physiology; Gene Expression Regulation, Fungal; Genes, Fungal/physiology; Membrane Glycoproteins/genetics; Membrane Glycoproteins/physiology; Mice; Mice, Inbred BALB C; Mutation; Proto-Oncogene Proteins c-bcr/genetics; Proto-Oncogene Proteins c-bcr/physiology; Rats; Rats, Sprague-Dawley

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CANAL:TEC1

acts_upstream_of_or_within

GO:0006355: regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:TEC1

acts_upstream_of_or_within

GO:0044011: single-species biofilm formation on inanimate substrate

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:TEC1

acts_upstream_of_or_within

GO:1900231: regulation of single-species biofilm formation on inanimate substrate

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:BCR1

involved_in

GO:1900231: regulation of single-species biofilm formation on inanimate substrate

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:BCR1

involved_in

GO:0044011: single-species biofilm formation on inanimate substrate

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CANAL:BCR1

involved_in

GO:0006355: regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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