Genetic Insights into the Rheological Strength of Candida albicans Biofilms
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ABSTRACT:
PROVIDER: PRJNA1157323 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30550805_1.fastq.gz | Fastqsanger.gz | |||
| SRR30550805_2.fastq.gz | Fastqsanger.gz | |||
| SRR30550806_1.fastq.gz | Fastqsanger.gz | |||
| SRR30550806_2.fastq.gz | Fastqsanger.gz | |||
| SRR30550807_1.fastq.gz | Fastqsanger.gz |
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Project description:The principal opportunistic human fungal pathogen Candida albicans forms biofilms resistant to antifungal therapeutics. Biofilms are a class of soft matter with viscoelastic properties and response to flow, but little is known regarding the genes contributing to these rheological phenotypes in fungal biofilms. Here, we identify C. albicans genes with deletion phenotypes of altered biofilm viscoelasticity. We analyzed mutants deleted for genes contributing to cell wall structure or extracellular matrix (ECM) production, and we identified increased elastic moduli, indicative of higher viscoelasticity, in strains singly deleted for PMR1, KRE5, and ALG11. PMR1 encodes a secretory pathway calcium pump. KRE5 encodes a UDP-glucose:glycoprotein glucosyltransferase, and ALG11 encodes alpha-1,2-mannosyltransferase. These mutants form less biofilm ECM by weight relative to wild type when cultured on agar. For these strains, biofilm morphology is smooth, with reduced hyphal formation. The mutants exhibit decreased resistance to the antifungal agent fluconazole relative to wild type biofilm cultures. To identify intracellular changes underlying these altered rheological properties, we globally profiled transcript levels in the respective mutants. Genes encoding membrane proteins were enriched in the set of transcripts differentially abundant in the alg11 deletion mutant. RNA levels are altered for genes associated with translation in the pmr1 deletion mutant and protein catabolism in the kre5 deletion strain. Genes involved in lipid metabolism and filamentous development are differentially expressed in cells from alg11, kre5, and pmr1 deletion mutant biofilms. Collectively, the data indicate C. albicans biofilm rheology as a phenotype affected by ECM production and cell morphology, while identifying genes for the investigation of mechanisms underlying properties of fungal biofilm viscoelasticity.
2024-10-21 | GSE276413 | GEO
Project description:Candida spp. are commensal opportunistic fungal pathogens that often colonize and infect mucosal surfaces of the human body. Candida, along with other microbes in the microbiota, generally grow as biofilms in a polymicrobial environment. Due to the nature of cellular growth in a biofilm (such as production of a protective extracellular matrix) and the recalcitrance of biofilms, infections involving biofilms are very difficult to treat with antibiotics and perpetuate the cycle of infection. The two most commonly isolated Candida spp. from Candida infections are Candida albicans and Candida glabrata, and the presence of both of these species results in increased patient inflammation and overall biofilm formation. This work aims to investigate the interspecies interactions between C. albicans (Ca) and C. glabrata (Cg) in co-culture through transcriptome analysis over the course of biofilm growth. We report that during co-culture, lipid biosynthesis and transporter genes were significantly modulated in both Ca and Cg. Differentially expressed genes in Ca during co-culture growth included putative transporter genes (C2_02180W_A and C1_09210C_B; up-regulated), amino acid biosynthesis (ARO7; up-regulated most in Ca:Cg 1:3), and lipid-related genes (LIP3 and IPT1; down-regulated). Differentially expressed genes in Cg in co-culture included putative transmembrane transporters (CAGL0H03399g and CAGL0K04609g; up-regulated), an oxidative stress response gene (CAGL0E04114g; down-regulated most in Ca:Cg 1:3), genes involved in the TCA cycle (LYS12 and CAGL0J06402g; down-regulated), and several genes involved in cell wall/membrane biosynthesis (SEC53, GAS2, VIG9; down-regulated). Additionally, confocal microscopy was utilized for membrane lipid analysis between monoculture and co-culture biofilms. Through filipin-stained lipid analysis, we found that there was a significant increase in cell membrane lipid content in Ca:Cg 1:3 biofilms compared to Ca and Ca:Cg 3:1 biofilms. These results suggest substantial modifications of both cell wall, cell membrane, and transporters in both Ca and Cg during the time course of co-culture growth, which allows for increased biofilm formation and virulence in Candida co-culture biofilms.
2019-05-31 | GSE119059 | GEO
Project description:Candida albicans is a commensal yeast within the human microbiota with significant medical importance because of its pathogenic potential. The yeast produces biofilms, which are highly resistant to available antifungals. High level of antifungal resistance by C. albicans biofilms has resulted in the need for alternative treatment. Polyunsaturated fatty acids such as arachidonic acid has been reported to increase the susceptibility of C. albicans biofilms to azole. However, the underlining mechanism is unknown. To unravel the mechanism behind this phenomenon, identification of differentially regulated genes in C. albicans biofilms grown in the presence of arachidonic acid, fluconazole, and the combination of both compounds was conducted using RNAseq.
2020-08-25 | GSE137423 | GEO
Project description:Candida albicans biofilms form complex structures that shield the fungus from antifungal agents and host immune responses, which is particularly problematic for the treatment of severe candidiasis. The increasing thickness and formation of hyphal networks of growing biofilms result in nutrient and gas shifts that lead to sequential metabolic rearrangements. This study provides very comprehensive insights into the molecular and metabolic mechanisms of C. albicans biofilm maturation by combining three state-of-the-art omics techniques. Adaptive nutrient and stress responses enabled wild type biofilms to mature in an increasingly nutrient- and oxygen-limited environment. C. albicans biofilms lacking Stp2, a transcriptional regulator of amino acid uptake, underwent extensive transcriptional changes resulting in metabolic adaptations such as broad restructuring of nitrogen metabolism, glucose uptake, and acquisition of alternative nutrients. This finding underscores the indispensable need for amino acid supply during biofilm development and emphasizes the tremendous metabolic flexibility to adapt to changing environments that have made C. albicans a successful opportunistic pathogen.
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Project description:The goals of this dual-seq experiment were to 1) identify transcriptional changes between mono-species and dual-species biofilms of Candida albicans and Pseudomonas aeruginosa and 2) identify transcriptional changes within mono- or dual-species P. aeruginosa biofilm cells in response to meropenem treatment.
2022-11-11 | GSE167137 | GEO
Project description:The interaction of clinically relevant microorganisms is the focus of various studies, e.g. the interaction between the pathogenic yeast, Candida albicans, and the bacterium, Pseudomonas aeruginosa and these interactions can alter the outcome of infection, growth dynamics of each species and antimicrobial resistance of pathogens. During infection, both C. albicans and P. aeruginosa can elicit the release arachidonic acid (AA) from host cells membranes through the action of phospholipases. This polyunsaturated fatty acid can be transformed into immune-modulating compounds, termed eicosanoids, by both host-derived and microbial-derived enzymatic reactions. In its free form, AA can affect the growth of both C. albicans and P. aeruginosa, inhibiting the morphogenesis of C. albicans as well as reducing resistance towards antifungal agents. However, the mechanism of this is unknown. Previous studies on the effect of polyunsaturated fatty acids have indicated a possible alteration in plasma membrane organisation and permeability. Our group aimed to address how AA affects C. albicans in both single species biofilms, as well as in polymicrobial biofilms with P. aeruginosa. RNAseq was performed on single and polymicrobial biofilms in the presence and absence of a sub-inhibitory (100 µM) concentration of AA. Differential expression was determined between C. albicans single species biofilms in the presence and absence of AA. Secondly, the influence of co-incubation of C. albicans with P. aeruginosa in the absence of AA was evaluated to identify novel facets of interaction not previously identified, and to establish a baseline to determine the effect of AA on C. albicans in polymicrobial biofilms. Lastly, the effect of AA on C. albicans in polymicrobial biofilms was determined through comparison with polymicrobial biofilms in the absence of AA. This study provides a comprehensive analysis of the effect of AA and both co-incubation of C. albicans with P. aeruginosa focused on the transcriptome.
2021-01-31 | GSE136726 | GEO
Project description:To explain enhanced biofilm formation and increased dissemination of S. epidermidis in mixed-species biofilms, microarrays were used to explore differential gene expression of S. epidermidis in mixed-species biofilms. One sample from single species biofilm (S1) and mixed-species biofilm (SC2) were excluded from analyses for outliers. We observed upregulation (2.7%) and down regulation (6%) of S. epidermidis genes in mixed-species biofilms. Autolysis repressors lrgA and lrgB were down regulated 36-fold and 27-fold respectively and was associated with increased eDNA possibly due to enhanced autolysis in mixed-species biofilms. These data suggest that bacterial autolysis and release of eDNA in the biofilm matrix may be responsible for enhancement and dissemination of mixed-species biofilms of S. epidermidis and C. albicans. Staphylococcal gene expression in mixed-species biofilms with Candida and in single species biofilms of S. epidermidis were analyzed. The experiment was repeated thrice on 3 different days (3 biological replicates each for single species biofilms of S. epidermidis and mixed-species biofilms). Only 2 biological replicates were analyzed and one biological replicate was not analyzed (S1 and SC1 - raw data files are provided on the Series record). Single species biofilms of S. epidermidis (strain 1457) and C. albicans (strain 32354) and mixed-species biofilms were formed on 6-well tissue culture plates. Five ml of organism suspensions (O.D. 0.3, S. epidermidis 107 CFU/ml or C. albicans 105 CFU/ml) or 2.5 ml each for mixed-species biofilms for 24 hr. RNA was harvested from single species and mixed-species biofilms.
2012-02-28 | E-GEOD-35438 | biostudies-arrayexpress
Project description:Transcriptional profiling of Candida albicans cells grown under planktonic and biofilm-inducing conditions, comparing SN76 and sfl1Δ/sfl1Δ strains. Goal was to study the effect of SFL1 deletion on the transcriptomic profile of C. albicans planktonic and biofilm cells under acidic conditions, in order to reveal the function of the Sfl1 transcription factor in C. albicans biofilm development.
2023-03-03 | GSE206208 | GEO
Project description:Biomaterial infections are an increasingly alarming problem, and because of their intrinsic recalcitrance to conventional therapy, a new class of antifungal drugs must be explored. 10b, a 2-aminotetralin derivate, was synthesized as a novel chemical structural antifungal agent and exibited strong anti-biofilm activity. To further investigate the action mechanism, we used microarray analysis to investigate the genes expression profiles of C. albicans biofilms treated or untreated with 10b and found 150 genes were differentially expressed. Of them, 69 showed a decrease in expression and 81 showed an increase in expression -10 differentially expressed genes related to biofilm formation, Filamentous or hypha growth. A gene related to specifically hydrolyzing β-1, 3 glucan was significantly increased. 10 down-regulated genes were involved in glycolysis, fermentation and active oxygen scavenging. 15 overexpressed genes were related to the lipid metabolic process. Of them, 13 genes were directly linked to ergosterol biosynthesis including ERG2, ERG6 and ERG11. 10 genes related to translation were over-expressed. Among them, 2 genes involved in negative regulation of transcription were significantly up-regulated. Total RNA from the control SC5314 biofilms and 10b-treated SC5314 biofilms were used to generate target cDNA, and then hybridized to 8k Candida albicans Genome Array Genechips, representing about 7925 characterized Candida albicans genes. Two independent experiments were conducted. Reference strain was control SC5314 biofilms and test strain was SC5314 biofilms treated with 10b.
2010-05-18 | E-GEOD-19226 | biostudies-arrayexpress
Project description:Genome-wide transcriptional profiles of Pseduomonas aerguinosa and Candida albicans after growth for 24 hours in mixed species colony biofilms.
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