Suppression of biofilm formation by Candida albicans and multispecies by nepodin of Rumex root via hyphal inhibition
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ABSTRACT:
ORGANISM(S): Candida albicans
PROVIDER: GSE119822 | GEO | 2021/09/01
REPOSITORIES: GEO
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Project description:Candida albicans is an opportunistic pathogen and responsible for candidiasis. C. albicans readily forms biofilms on various biotic and abiotic surfaces, and these biofilms can cause local and systemic infections. C. albicans biofilms are more resistant than its free yeast to antifungal agents and less affected by host immune responses. Transition of yeast cells to hyphal cells is required for biofilm formation and is believed to be a crucial virulence factor. In this study, six components of ginger were investigated for antibiofilm and antivirulence activities against a fluconazole-resistant C. albicans strain. It was found 6-gingerol, 8-gingerol, and 6-shogaol effectively inhibited biofilm formation. In particular, 6-shogaol at 10 µg/ml significantly reduced C. albicans biofilm formation but had no effect on planktonic cell growth. Also, 6-gingerol and 6-shogaol inhibited hyphal growth in embedded colonies and free-living planktonic cells, and prevented cell aggregation. Furthermore, 6-gingerol and 6-shogaol reduced C. albicans virulence in a nematode infection model without causing toxicity at the tested concentrations. Transcriptomic analysis using RNA-seq and qRT-PCR showed 6-gingerol and 6-shogaol induced several transporters (CDR1, CDR2, and RTA3), but repressed the expressions of several hypha/biofilm related genes (ECE1 and HWP1), which supported observed phenotypic changes. These results highlight the antibiofilm and antivirulence activities of the ginger components, 6-gingerol and 6-shogaol, against a drug resistant C. albicans strain.
2018-12-25 | GSE117201 | GEO
Project description:C. albicans is a dimorphic yeast which can switch from budding yeast and to hyphal forms and this property is essential for biofilm establishment and maturation. C. albicans undergoes this yeast-to-hyphal switch in response to high CO2. The purpose of this study is to use RNA-seq to investigate pathways whose genes are differentially expressed when C. albicans biofilms are grown in a physiologically relevant elevated (5%) CO2 environment compared to a low/atmospheric (0.03%) CO2 environment. We report that in C.albicans biofilms grown under 5% CO2 conditions, genes controlled by core biofilm regulatory transcription factors such as Brg1, Efg1, Ndt80, and Bcr1 are overall expressed at significantly higher levels compared to those grown in 0.03% CO2 conditions. We find that genes encoding glucose and amino acid transporters, as well as genes previously found to be involved in the response to Ketoconazole treatment, are significantly upregulated in 5% CO2 C. albicans biofilms. Overall, these data suggest a high CO2 environment enhances biofilm formation of C. albicans and may also increase antifungal tolerance of such biofilms.
2021-04-14 | GSE172004 | 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.
2022-10-13 | PXD026449 | Pride
Project description:Biofilms are a communal of one or several kinds of microorganisms that growing on of both non-living and biotic surfaces by the production of multi-layers high-abundance extracellular matrix (ECM) to survive in the harsh environments (1-4). Biofilms consist of 85% (by volume) of matrix materials and 15% microbial cells (5). Biofilm ECM, consists of proteins, polysaccharides and/or extracellular DNAs, is important for biofilm integrity that increases environmental adaptability and induces antimicrobial resistance (6-7). Surface-adherent (sessile) bacteria in biofilms are more difficult to eradicate as minimum inhibitory concentrations (MICs) of antibiotics against bacterial biofilms is 100-1000 folds higher than the free living (planktonic) form that resulting in recurrent infections (8). Biofilms also possibly form nidus at the surface for the attachment of other pathogens lead to biofilms of multiple bacteria or multi-organisms (9ref). The communication, among organisms within biofilm, controls density of cell population refers to as “quorum sensing” (10) and different combinations of organisms in biofilms with either multiple bacteria or multi-species might induce different biofilm properties. While catheter-related colonization of Gram-positive bacteria from skin microbiota such as Streptococcus spp. and Staphylococcus spp. is common, biofilms in the inner lumen of catheter consist of both Gram-positive and Gram-negative bacteria. Because i) translocation of gut microbiota (eg. Enterococcus spp., Gram-negative bacteria and Candida albicans) into blood circulation during sepsis is one of the common causes of severe sepsis , ii) mixed systemic infection between bacteria and Candida spp. is even more severe than the infection by each organism in separation and iii) biofilms could be formed during bacteremia and fungemia, the biofilms from mixed species between bacteria and Candida spp. during sepsis is possible. In addition, central venous catheter-related candidiasis is common in intensive care units (ICU) patients refer to as “Candida catheter-related bloodstream infection (CRCBSI)”. Moreover, synergistic interaction between Candida albicans and several Gram-negative bacteria such as Escherichia coli (in peritonitis), Pseudomonas aeruginosa (in cystic fibrosis and ventilation associated pneumonia) and Acinetobacter baumannii (in ventilation associated pneumonia) has been mentioned. Hence, the collaboration between bacteria and Candida spp. might affect biofilm production as C. albicans in coexistence with the sessile microbes possibly enhance biofilms production that is detectable by crystal violet color (16,7). It is interesting to note that C. albicans are normal microbiota in human intestine and gut-translocation from intestine into blood circulation during severe sepsis (gut leakage) is demonstrated. Furthermore, both Gram-negative bacteria and C. albicans are the most and the second most predominant intestinal human microbiota, respectively, in which the natural interactions between these organisms is possible. Accordingly, catheter-related bacteremia is common among patients in ICU. Gut translocation of Candida spp. during sepsis, due to gut leakage, might induce the collaboration between bacteria and fungi results in persistent infection (20-21Chen L, 2011, 66//Wu H, 2015, 1, IJOS). Although the understanding in the interaction between organisms in biofilms should be beneficial for eradication strategies, the data of biofilms from the combination between gut-derived bacteria and fungi is still limited. As such, production of exo-polymers for biofilm-forming is a pathogenic virulent factor because biofilms is one of the important defend-mechanisms against host immune responses and antibiotics. Because i) antibiotic resistance caused by biofilm is a current serious medical problem , ii) the eradication of both bacterial and fungal biofilms is difficult and iii) antimicrobial treatment without biofilms-removal resulting in recurrent or persistent infection (23ref), biofilm prevention agent is needed (2410). Here, we explored i) the interaction between Gram-negative bacteria and C. albicans, in vitro, ii) macrophage responses against biofilm components, iii) biofilms in catheter-insertion mouse model and an evaluation on an interesting anti-biofilm.
2021-09-09 | PXD020949 | Pride
Project description:Due to the great challenge in treating biofilms, there is an urgent need for novel and effective antibiofilm compounds. Through bioassay-guided isolation of bioactive compounds from Actinobacteria, we identified elasnin as a potent biofilm-targeting compound against methicillin-resistant Staphylococcus aureus (MRSA). Elasnin effectively inhibited biofilm formation and eradicated pre-formed biofilms of MRSA. To gain more insights on how elasnin eradicate MRSA biofilms, we conducted proteomics study on MRSA biofilm cells under elasnin treatment compared to the untreated cells.
2022-07-22 | PXD026836 | Pride
Project description:Candida albicans is an opportunistic fungal pathogen that can infect oral mucosal surfaces despite being under continuous flow from saliva. Previous studies have shown that under specific conditions C. albicans will form microcolonies that more closely resemble the biofilms formed in vivo than standard in vitro biofilm models. However, very little is known about these microcolonies, particularly genomic differences between these specialized biofilm structures and the traditional in vitro biofilms. In this study, we used a novel flow system, in which C. albicans spontaneously forms microcolonies, to further characterize the architecture of fungal microcolonies and their genomics compared to non-microcolony conditions. Fungal microcolonies arise from radially branching filamentous hyphae that increasingly intertwine with one another to form extremely dense biofilms, and closely resemble the architecture of in vivo oropharyngeal candidiasis. We identified 20 core microcolony genes that were differentially regulated in flow-induced microcolonies using RNA-seq. These genes included HWP1, ECE1, IHD1, PLB1, HYR1, PGA10, and SAP5. To better understand the regulatory elements for microcolonies, we utilized a predictive algorithm to discover ten transcriptional regulators potentially involved in microcolony formation. Of these transcription factors, we found that six played a key role in microcolony formation and development (Rob1, Ndt80, Efg1, Sfl1, Sfl2, and Nrg1). We also found that Hwp1, Sap5, Pga10, and all the microcolony regulators promoted adhesion and invasion of the microcolonies to oral epithelium. Furthermore, epithelial cells infected with deletion mutants of ROB1, NDT80, SFL2, EFG1, and MCM1 had reduced immune response, evidenced by reduced phosphorylation of MKP1 and c-Fos, key signal transducers in the hyphal invasion response. This profile of microcolony transcriptional regulators more closely reflects Sfl1 and Sfl2 hyphal regulatory networks than biofilm regulatory networks, suggesting that hyphal morphogenesis plays a more central role in the development of flow-induced microcolonies.
2018-07-21 | GSE117433 | GEO
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 albicans can stochastically switch between two phenotypes, white and opaque. Opaque cells are the sexually competent form of C. albicans and therefore undergo efficient polarized growth and mating in the presence of pheromone. In contrast, white cells cannot mate, but are induced - under a specialized set of conditions - to form biofilms in response to pheromone. In this work, we compare the genetic regulation of such "pheromone-stimulated" biofilms with that of "conventional" C. albicans biofilms. In particular, we examined a network of six transcriptional regulators (Bcr1, Brg1, Efg1, Tec1, Ndt80, and Rob1) that mediate conventional biofilm formation for their potential roles in pheromone-stimulated biofilm formation. We show that four of the six transcription factors (Bcr1, Brg1, Rob1, and Tec1) promote formation of both conventional and pheromone-stimulated biofilms, indicating they play general roles in cell cohesion and biofilm development. In addition, we identify the master transcriptional regulator of pheromone-stimulated biofilms as C. albicans Cph1, ortholog of Saccharomyces cerevisiae Ste12. Cph1 regulates mating in C. albicans opaque cells, and here we show that Cph1 is also essential for pheromone-stimulated biofilm formation in white cells. In contrast, Cph1 is dispensable for the formation of conventional biofilms. The regulation of pheromone- stimulated biofilm formation was further investigated by transcriptional profiling and genetic analyses. These studies identified 206 genes that are induced by pheromone signaling during biofilm formation. One of these genes, HGC1, is shown to be required for both conventional and pheromone-stimulated biofilm formation. Taken together, these observations compare and contrast the regulation of conventional and pheromone-stimulated biofilm formation in C. albicans, and demonstrate that Cph1 is required for the latter, but not the former.
2013-02-22 | GSE44449 | 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: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