Functional Dichotomy for a Hyphal Repressor in Candida albicans

Mao, Yixin; Solis, Norma V.; Filler, Scott G.; Mitchell, Aaron P.

doi:10.1128/mbio.00134-23

Cited by 8 publications

(2 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The X and Y axes represent efg1 Δ/Δ vs wild-type log fold change for SC5314 and P57055, respectively. The data sets correlate with R 2 = 0.78. d) Regression analysis shows the number of significantly regulated ( P < 0.05) NRG1 -responsive genes, regardless of fold change, from previously published data ( Mao et al . 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Strain variation in gene expression impact of hyphal cyclin Hgc1 in Candida albicans

Sharma

Mitchell

2023

G3: Genes, Genomes, Genetics

Self Cite

View full text Add to dashboard Cite

Formation of hyphae is a key virulence trait of the fungal pathogen Candida albicans. Hypha morphogenesis depends upon the cyclin Hgc1, which acts together with cyclin-dependent protein kinase Cdc28 to phosphorylate effectors that drive polarized growth. Hgc1 has also been implicated in gene regulation through its effects on two transcription factors, Efg1 and Ume6. Here we report RNA-seq analysis of two pairs of hgc1Δ/Δ mutants and their respective wild-type strains, which lie in two different genetic backgrounds. We find that hgc1Δ/Δ mutations alter expression of 271 genes in both genetic backgrounds, and 266 of those genes respond consistently with regard to up- or down-regulation. Consistency is similar to what has been observed with efg1Δ/Δ mutations and greater than observed with nrg1Δ/Δ mutations in these two backgrounds. The gene expression response includes genes under Efg1 control, as expected from prior studies. Hgc1-responsive genes also include ergosterol biosynthetic genes and bud neck-related genes, which may reflect interactions between Hgc1 and additional transcription factors as well as effects of Hgc1 on cellular length-to-width ratios.

show abstract

Section: Resultsmentioning

confidence: 99%

Strain variation in gene expression impact of hyphal cyclin Hgc1 in Candida albicans

Sharma

Mitchell

2023

G3: Genes, Genomes, Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Large karyotypic changes, such as Chr4 trisomy, can promote antifungal drug resistance in some strains but have no effect in others [ 30 ]. Furthermore, genetic backgrounds respond differently to targeted deletion of central transcriptional regulators of biofilm formation [ 4 31 ]. For example, bcr1 Δ/Δ cells in the P57055 strain fail to form biofilms, whereas deletion of BCR1 in SC5314 minimally alters biofilm mass, biofilm architecture and transition between yeast and hyphal cell states.…”

Section: Introductionmentioning

confidence: 99%

Strain background of Candida albicans interacts with SIR2 to alter phenotypic switching

Woodruff,

Berman,

Anderson

2024

Microbiology

View full text Add to dashboard Cite

The genetic background between strains of a single species and within a single strain lineage can significantly impact the expression of biological traits. This genetic variation may also reshape epigenetic mechanisms of cell identity and environmental responses that are controlled by interconnected transcriptional networks and chromatin-modifying enzymes. Histone deacetylases, including sirtuins, are critical regulators of chromatin state and have been directly implicated in governing the phenotypic transition between the ‘sterile’ white state and the mating-competent opaque state in Candida albicans, a common fungal commensal and pathogen of humans. Here, we found that a previously ambiguous role for the sirtuin SIR2 in C. albicans phenotypic switching is likely linked to the genetic background of mutant strains produced in the RM lineage of SC5314. SIR2 mutants in a specific lineage of BWP17 displayed increased frequencies of switching to the opaque state compared to the wild-type. Loss of SIR2 in other SC5314-derived backgrounds, including newly constructed BWP17 sir2Δ/Δ mutants, failed to recapitulate the increased white–opaque switching frequencies observed in the original BWP17 sir2Δ/Δ mutant background. Whole-genome sequencing revealed the presence of multiple imbalanced chromosomes and large loss of heterozygosity tracts that likely interact with SIR2 to increase phenotypic switching in this BWP17 sir2Δ/Δ mutant lineage. These genomic changes are not found in other SC5314-derived sir2Δ/Δ mutants that do not display increased opaque cell formation. Thus, complex karyotypes can emerge during strain construction that modify mutant phenotypes and highlight the importance of validating strain background when interpreting phenotypes.

show abstract

Blood cultures contain populations of genetically diverseCandida albicansstrains that may differ in echinocandin tolerance and virulence

Fleres,

Cheng,

Badrane

et al. 2024

Preprint

View full text Add to dashboard Cite

It is unknown whether within-patient Candida albicans diversity is common during bloodstream infections (BSIs). We determined whole genome sequences of 10 C. albicans strains from blood cultures (BCs) at baseline (n=4 patients) and during persistent BSIs (3 of 4 patients). BCs contained mixed populations of strains that differed by single nucleotide polymorphisms (n=4 patients), chromosome (Chr) 5 or 7 aneuploidy (n=2), and loss of heterozygosity (n=1). Chr7 trisomy (Tri7) strains from patient MN were attenuated for hyphal and biofilm formation in vitro compared to euploid strains, due to NRG1 over-expression. However, Tri7 strain M1 underwent filamentation during disseminated candidiasis (DC) in mice. M1 was more fit than euploid strain M2 during DC and gastrointestinal colonization/infection, and in blood ex vivo. M1 and M2 exhibited identical echinocandin minimum inhibitory concentrations, but M2 was more tolerant to micafungin in vitro. Furthermore, M2 was more competitive with M1 in mouse kidneys following micafungin treatment than it was in absence of micafungin. Tri7 strains represented 74% of patient MN’s baseline BC population, but after 1d and 3d of echinocandin treatment, euploid strains were 93% and 98% of the population, respectively. Findings suggest that echinocandin tolerant, euploid strains were a subpopulation to more virulent Tri7 strains at baseline and then selected upon echinocandin exposure. In conclusion, BCs in at least some patients are comprised of diverse C. albicans populations not recognized by the clinical lab, rather than single, genetically and phenotypically identical strains. Clinical relevance of C. albicans diversity and antifungal tolerance merits further investigation.

show abstract

Functional Dichotomy for a Hyphal Repressor in Candida albicans

Abstract: Hypha formation is a central virulence trait of the fungal pathogen Candida albicans . Control of hypha formation has been studied in detail in the type strain but not in other diverse C. albicans clinical isolates.

Cited by 8 publications

References 32 publications

Strain variation in gene expression impact of hyphal cyclin Hgc1 in Candida albicans

Strain variation in gene expression impact of hyphal cyclin Hgc1 in Candida albicans

Strain background of Candida albicans interacts with SIR2 to alter phenotypic switching

Blood cultures contain populations of genetically diverseCandida albicansstrains that may differ in echinocandin tolerance and virulence

Contact Info

Product

Resources

About