An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype

Delaney, Christopher; Short, Bryn; Rajendran, Ranjith; Kean, Ryan; Burgess, Karl; Williams, Craig; Munro, Carol A.; Ramage, Gordon

doi:10.1016/j.bioflm.2023.100112

Cited by 5 publications

(6 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In S. cerevisiae , nine genes ( ARO3 , ARO1 , ARO2 , ARO7 , PHA2 , ARO8 , ARO10 , ADH , and PDR12 ) and the Ssy1p membrane protein (encoded by the SSY1 gene) have been identified to be involved in 2-PE synthesis (Delaney et al 2023 ; Hazelwood et al 2008 ; Larroude et al 2021 ; Zhu et al 2021 ). The first five genes ( ARO3 , ARO1 , ARO2 , ARO7 , and PHA2 ) play important roles in the pathway and are primarily responsible for the conversion of glucose to phenylpyruvate.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive investigations of 2-phenylethanol production by the filamentous fungus Annulohypoxylon stygium

Tong,

Yang,

Zhang

et al. 2024

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

2-Phenylethanol (2-PE) is an aromatic compound with a rose-like fragrance that is widely used in food and other industries. Yeasts have been implicated in the biosynthesis of 2-PE; however, few studies have reported the involvement of filamentous fungi. In this study, 2-PE was detected in Annulohypoxylon stygium mycelia grown in both potato dextrose broth (PDB) and sawdust medium. Among the 27 A. stygium strains investigated in this study, the strain “Jinjiling” (strain S20) showed the highest production of 2-PE. Under optimal culture conditions, the concentration of 2-PE was 2.33 g/L. Each of the key genes in Saccharomyces cerevisiae shikimate and Ehrlich pathways was found to have homologous genes in A. stygium. Upon the addition of L-phenylalanine to the medium, there was an upregulation of all key genes in the Ehrlich pathway of A. stygium, which was consistent with that of S. cerevisiae. A. stygium as an associated fungus provides nutrition for the growth of Tremella fuciformis and most spent composts of T. fuciformis contain pure A. stygium mycelium. Our study on the high-efficiency biosynthesis of 2-PE in A. stygium offers a sustainable solution by utilizing the spent compost of T. fuciformis and provides an alternative option for the production of natural 2-PE. Key points • Annulohypoxylon stygium can produce high concentration of 2-phenylethanol. • The pathways of 2-PE biosynthesis in Annulohypoxylon stygium were analyzed. • Spent compost of Tremella fuciformis is a potential source for 2-phenylethanol.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Ssy1p is a membrane protein with a function to import L-Phe from the extracellular environment (Delaney et al 2023 ). It is encoded by the member of the family of amino acid transporter genes, SSY1 (Didion et al 1998 ).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive investigations of 2-phenylethanol production by the filamentous fungus Annulohypoxylon stygium

Tong,

Yang,

Zhang

et al. 2024

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…Metabolomic analysis is well suited to develop a global understanding of the differences between planktonic and biofilm physiology. However, one detailed study found a limited correlation between strains and conditions [ 46 ], noting that biofilm cell heterogeneity is extensive. For this reason, we consider genetic approaches to be an important complement to metabolomic strategies.…”

Section: Discussionmentioning

confidence: 99%

Biofilm-associated metabolism via ERG251 in Candida albicans

Xiong,

Pereira De Sa,

Zarnowski

et al. 2024

PLoS Pathog

View full text Add to dashboard Cite

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 erg251Δ/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 erg251Δ/Δ mutation causes defects in growth and hyphal extension. Overexpression in the erg251Δ/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 erg251Δ/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 erg251Δ/Δ mutant causes some increase in ergosterol levels. Finally, the hypersensitivity of efg1Δ/Δ mutants to the ergosterol inhibitor fluconazole is reversed by ERG251 overexpression, arguing that reduced ERG251 expression contributes to this efg1Δ/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.

show abstract

“…A radical shift in gene expression and cellular metabolism has been reported in bacteria and fungi during the transition from planktonic to community growth. Bacterial and fungal biofilms indeed show unique metabolic patterns, such as differential expression of glycolytic pathway and TCA cycle genes, indicating significant metabolic reprogramming during microbial biofilm development [45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Metabolic reprogramming during Candida albicans planktonic-biofilm transition is modulated by the transcription factors Zcf15 and Zcf26

Rai,

Chauvel,

Sanchez

et al. 2024

PLoS Biol

View full text Add to dashboard Cite

Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulating C. albicans biofilm formation, we performed a large-scale screen with 2,454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their role in reprogramming cellular metabolism by regulating central metabolism including glyoxylate and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling.

show abstract

An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype

Cited by 5 publications

References 71 publications

Comprehensive investigations of 2-phenylethanol production by the filamentous fungus Annulohypoxylon stygium

Comprehensive investigations of 2-phenylethanol production by the filamentous fungus Annulohypoxylon stygium

Biofilm-associated metabolism via ERG251 in Candida albicans

Metabolic reprogramming during Candida albicans planktonic-biofilm transition is modulated by the transcription factors Zcf15 and Zcf26

Contact Info

Product

Resources

About