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: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:Biofilm formation on medically implanted devices by Candida albicans poses a significant clinical challenge. Here we compared biofilm-associated gene expression in two clinical C. albicans isolates, SC5314 and WO-1, to identify shared gene regulatory responses that may be functionally relevant. Among the 50 genes most highly expressed in biofilms relative to planktonic (suspension-grown) cells, we were able to recover insertion mutations in 25 genes. We observed that 20 of the 25 mutants have altered biofilm-related properties, including cell-substrate adherence, cell-cell signaling, and azole susceptibility. We focused on the most highly up-regulated gene in biofilms, RHR2, which specifies the glycerol biosynthetic enzyme glycerol-3-phosphate phosphatase. Glycerol is 5-fold more abundant in biofilm cells than planktonic cells, and an rhr2D/D strain accumulates 2-fold less biofilm glycerol than the wild type. Under in vitro growth conditions, the rhr2D/D mutant has reduced biofilm biomass and reduced adherence to silicone. The rhr2D/D mutant is severely defective in biofilm formation in vivo, in a rat catheter infection model. Expression profiling of the rhr2D/D mutant indicates that it has reduced expression of cell surface adhesin genes ALS1, ALS3, and HWP1, as well as a large fraction of all other biofilm up-regulated genes. Reduced adhesin expression is the cause of the rhr2D/D mutant biofilm defect, because overexpression of ALS1, ALS3, or HWP1 restores biofilm formation ability to the mutant in vitro and in vivo. Our findings indicate that internal glycerol has a regulatory role in biofilm gene expression, and that adhesin genes are among the main functional Rhr2-regulated genes. Gene expression profiles, in duplicate; (1) for biofilm vs. planktonic growth conditions for the two wild-type clinical isolates of Candida albicans (SC5314 and WO1-white/WO1-opaque), and (2) for rhr2M-NM-^T/M-NM-^T mutant and complemented strain, via RNA-deep sequencing using Illumina GA2 and HiSeq2000 platforms, respectively
2013-04-12 | E-GEOD-45141 | biostudies-arrayexpress
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:Biofilm formation on medically implanted devices by Candida albicans poses a significant clinical challenge. Here we compared biofilm-associated gene expression in two clinical C. albicans isolates, SC5314 and WO-1, to identify shared gene regulatory responses that may be functionally relevant. Among the 50 genes most highly expressed in biofilms relative to planktonic (suspension-grown) cells, we were able to recover insertion mutations in 25 genes. We observed that 20 of the 25 mutants have altered biofilm-related properties, including cell-substrate adherence, cell-cell signaling, and azole susceptibility. We focused on the most highly up-regulated gene in biofilms, RHR2, which specifies the glycerol biosynthetic enzyme glycerol-3-phosphate phosphatase. Glycerol is 5-fold more abundant in biofilm cells than planktonic cells, and an rhr2D/D strain accumulates 2-fold less biofilm glycerol than the wild type. Under in vitro growth conditions, the rhr2D/D mutant has reduced biofilm biomass and reduced adherence to silicone. The rhr2D/D mutant is severely defective in biofilm formation in vivo, in a rat catheter infection model. Expression profiling of the rhr2D/D mutant indicates that it has reduced expression of cell surface adhesin genes ALS1, ALS3, and HWP1, as well as a large fraction of all other biofilm up-regulated genes. Reduced adhesin expression is the cause of the rhr2D/D mutant biofilm defect, because overexpression of ALS1, ALS3, or HWP1 restores biofilm formation ability to the mutant in vitro and in vivo. Our findings indicate that internal glycerol has a regulatory role in biofilm gene expression, and that adhesin genes are among the main functional Rhr2-regulated genes.
2013-04-12 | GSE45141 | GEO
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 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:Introduction: Combined infections from Candida albicans and Staphylococcus aureus are a leading cause of death in the developed world. Evidence suggests that Candida enhances the virulence of Staphylococcus - hyphae penetrate through tissue barriers, while S. aureus tightly associates with the hyphae to obtain entry to the host organism. Indeed, in a biofilm state, C. albicans enhances the antimicrobial resistance characteristics of S. aureus. The association of these microorganisms is also associated with significantly increased morbidity and mortality. Due to this tight association we hypothesised that metabolic effects were also in evidence.</br> Objectives: To explore the interaction, we used a novel GC-Orbitrap – based mass spectrometer, the QExactive GC, which combines the high peak capacity and chromatographic resolution of gas chromatography with the sub-ppm mass accuracy of an Orbitrap system. This allows the capability to leverage the widely available electron ionisation libraries for untargeted applications, along with expanding accurate mass libraries and targeted matches based around authentic standards.</br> Methods: Optimised C. albicans and S. aureus mono- and co-cultured biofilms were analysed in addition to the fresh and spent bacterial growth media.</br> Results: The targeted analysis experiment was based around 36 sugars and sugar phosphates, 22 amino acids and five organic acids. We detected an additional 22 highly scoring compounds from untargeted analysis.</br> Conclusion: Many of the results were as expected – rapid consumption of glucose and fructose from the medium regardless of the cell type. We also detected trehalose from the untargeted data, only in medium that contained C. albicans, commensurate with it being a predominantly fungal sugar. Notable from the results is that the pentose phosphate pathway appears to be enhanced in the cells from co-cultured biofilms.
2017-02-20 | MTBLS370 | MetaboLights