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A Brg1-Rme1 circuit in Candida albicans hyphal gene regulation.
- Source :
-
MBio [mBio] 2024 Sep 11; Vol. 15 (9), pp. e0187224. Date of Electronic Publication: 2024 Jul 30. - Publication Year :
- 2024
-
Abstract
- Major Candida albicans virulence traits include its ability to make hyphae, to produce a biofilm, and to damage host cells. These traits depend upon expression of hypha-associated genes. A gene expression comparison among clinical isolates suggested that transcription factor Rme1 , established by previous studies to be a positive regulator of chlamydospore formation, may also be a negative regulator of hypha-associated genes. Engineered RME1 overexpression supported this hypothesis, but no relevant rme1 Δ/Δ mutant phenotype was detected. We reasoned that Rme1 may function within a specific regulatory pathway. This idea was supported by our finding that an rme1 Δ/Δ mutation relieves the need for biofilm regulator Brg1 in biofilm formation. The impact of the rme1 Δ/Δ mutation is most prominent under static or "biofilm-like" growth conditions. RNA sequencing (RNA-seq) of cells grown under biofilm-like conditions indicates that Brg1 activates hypha-associated genes indirectly via repression of RME1 : hypha-associated gene expression levels are substantially reduced in a brg1 Δ/Δ mutant and partially restored in a brg1 Δ/Δ rme1 Δ/Δ double mutant. An rme1 Δ/Δ mutation does not simply bypass Brg1, because iron homeostasis genes depend upon Brg1 regardless of Rme1. Rme1 thus connects Brg1 to the targets relevant to hypha and biofilm formation under biofilm growth conditions.IMPORTANCE Candida albicans is a major fungal pathogen of humans, and its ability to grow as a surface-associated biofilm on implanted devices is a common cause of infection. Here, we describe a new regulator of biofilm formation, RME1 , whose activity is most prominent under biofilm-like growth conditions.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- DNA Helicases genetics
DNA Helicases metabolism
Virulence genetics
Mutation
Candida albicans genetics
Candida albicans physiology
Gene Expression Regulation, Fungal
Fungal Proteins genetics
Fungal Proteins metabolism
Hyphae genetics
Hyphae growth & development
Biofilms growth & development
Transcription Factors genetics
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2150-7511
- Volume :
- 15
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- MBio
- Publication Type :
- Academic Journal
- Accession number :
- 39078139
- Full Text :
- https://doi.org/10.1128/mbio.01872-24