Biofilm-associated metabolism via ERG251 in Candida albicans

• Published in: PLoS pathogens Vol. 20; no. 5; p. e1012225
• Main Authors: Xiong, Liping, Pereira De Sa, Nivea, Zarnowski, Robert, Huang, Manning Y., Mota Fernandes, Caroline, Lanni, Frederick, Andes, David R., Del Poeta, Maurizio, Mitchell, Aaron P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.05.2024; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antifungal agents; Biofilms; Biofilms - growth & development; Biology and Life Sciences; Candida albicans; Candida albicans - genetics; Candida albicans - metabolism; Candida albicans - physiology; Candidiasis; Candidiasis - metabolism; Candidiasis - microbiology; Care and treatment; Catheters; Cell number; Control; Defects; Diagnosis; Dosage and administration; Drug resistance; Electronics industry; Engineering and Technology; Ergosterol; Ergosterol - metabolism; Fluconazole; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene expression; Gene Expression Regulation, Fungal; Genetic transcription; Health aspects; Hypersensitivity; Hyphae - metabolism; Hypotheses; Hypoxia; Identification and classification; Infection; Infections; Medical equipment; Medical instruments; Medicine and Health Sciences; Metabolism; Metabolites; Mice; Microbial mats; Mutants; Mutation; Phenotypes; Physiological aspects; Phytosterols; Plant lipids; Proteins; Research and Analysis Methods; Scanning electron microscopy; Statistical analysis; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Virulence; Yeast; United States; Japan
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012225

Biofilm formation by the fungal pathogen Candida albicans is the basis for its ability to infect medical devices. The metabolic gene ERG251 has been identified as a target of biofilm transcriptional regulator Efg1, and here we report that ERG251 is required for biofilm formation but not conventional free-living planktonic growth. An erg251 Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo catheter infection model. In both in vitro and in vivo biofilm contexts, cell number is reduced and hyphal length is limited. To determine whether the mutant defect is in growth or some other aspect of biofilm development, we examined planktonic cell features in a biofilm-like environment, which was approximated with sealed unshaken cultures. Under those conditions, the erg251 Δ/Δ mutation causes defects in growth and hyphal extension. Overexpression in the erg251 Δ/Δ mutant of the paralog ERG25 , which is normally expressed more weakly than ERG251 , partially improves biofilm formation and biofilm hyphal content, as well as growth and hyphal extension in a biofilm-like environment. GC-MS analysis shows that the erg251 Δ/Δ mutation causes a defect in ergosterol accumulation when cells are cultivated under biofilm-like conditions, but not under conventional planktonic conditions. Overexpression of ERG25 in the erg251 Δ/Δ mutant causes some increase in ergosterol levels. Finally, the hypersensitivity of efg1 Δ/Δ mutants to the ergosterol inhibitor fluconazole is reversed by ERG251 overexpression, arguing that reduced ERG251 expression contributes to this efg1 Δ/Δ phenotype. Our results indicate that ERG251 is required for biofilm formation because its high expression levels are necessary for ergosterol synthesis in a biofilm-like environment.