Manganese homeostasis modulates glucan and chitin unmasking in Candida albicans
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PROVIDER: PRJNA1196367 | ENA |
REPOSITORIES: ENA
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Project description:In our previous work, we generated a mutant of the Mn NRAMP transporter, smf12, to investigate the impact of Mn scarcity on the biology of C. albicans. We found that inactivation of SMF12 resulted in attenuated virulence, increased sensitivity to azoles, and activation of the unfolded protein response (UPR). To investigate further cellular processes affected in smf12, we carried out RNA-seq profiling under manganese (Mn) starvation. The transcriptional profile of smf12 growing in the Mn-free SC medium (SC-Mn) was compared to that of the WT strain growing under similar conditions. Upregulated transcripts in smf12 were mainly enriched in processes related to the synthesis and the processing of the three core polysaccharides of the fungal cell wall namely chitin (CHS2, 7, CDA2, CHT4), glucan (KRE1, 9, UTR2, PNG2) and phosphomannan (MNN1, 15, 41, 42, 43, 45, 47, BMT3, 4, 6, 7, KTR4, DFG5, FAV3). Transcripts related to cell wall signaling proteins and transcriptional control including the Cek1 MAP kinase, the histidine kinase Chk1 and the transcription factor Crz1 were also upregulated. This transcriptional signature is reminiscent of a situation in which the cell wall is undergoing remodeling in response to a specific perturbation.
2024-12-31 | GSE283948 | GEO
Project description:Candida albicans is a commensal yeast of the human gut, which is tolerated by the immune system, but has the potential to become an opportunistic pathogen. One way in which C. albicans achieves this duality is through the concealing, or exposure of cell wall associated pathogen-associated molecular patterns (PAMPs) in response to host derived environment cues (pH, hypoxia, lactate). This cell wall remodelling allows C. albicans to evade or hyperactivate the host’s innate immune responses leading to disease. Previously we identified that adaptation of C. albicans to acidic environments, conditions encountered during colonisation of the female reproductive tract, induce significant cell wall remodelling resulting in the exposure of two key fungal PAMPs (glucan and chitin). Here we report that this pH-dependent cell wall remodelling is a highly dynamic process, requiring periods of both cell wall unmasking, with peak PAMP exposure occurring between 2-4 hrs, followed by subsequent PAMP remasking. b-glucan remasking was mediated via the cell density dependent fungal quorum sensing molecule farnesol, while chitin remasking was mediated via a small, heat-stable, non-proteinaceous secreted molecule(s). Transcript profiling identified a core set of 42 genes significantly regulated by pH over time, and linked the transcription factor Efg1p to being the main regulator of chitin exposure through regulation of CHT2. This dynamic cell wall remodelling, influenced innate immune recognition of C. albicans, suggesting that during infection C. albicans can manipulate the host innate immune responses.
2019-10-16 | GSE130948 | GEO
Project description:Manganese homeostasis modulates fungal virulence and stress tolerance in Candida albicans
| PRJNA1026965 | ENA
Project description:RNA sequencing was performed on Candida albicans clinical isolates that display normal (isolates: 3560, 3605, 3609, 4108, 4259) or aberrant (isolates: 3534, 3544, 3621, 3636, 4036) beta-glucan masking in response to lactate and hypoxia. Each clinical isolate was grown to exponential phase in GYNB under normoxic conditions and then exposed for 5 h to: (a) 1% lactate; (b) 0% lactate control; (c) hypoxia; or (d) normoxic control. Three independent experiments were performed for each clinical isolate.
2023-09-05 | E-MTAB-10986 | biostudies-arrayexpress
Project description:Transcriptional profiling of B. japonicum manganese responsive cells and mur mutant responsive cells 3 independent biological materials were prepared for Wt manganese deplete, replete cultured cells and mur mutant manganese replete cultured cells
2011-08-24 | E-GEOD-30932 | biostudies-arrayexpress
Project description:As transition metal availability is very limited inside the human host, fungal pathogens have evolved sophisticated mechanisms to uptake and utilize these micronutrients at the infection interface. While considerable attention was turned into iron, copper and zinc acquisition mechanisms and their importance in fungal fitness, less was done regarding either the role of Mn in infectious processes or the cellular mechanism by which fungal cells achieve their Mn-homeostasis. Here, we undertook a transcriptional profiling of the pathogenic fungus Candida albicans experiencing both Mn starvation and excess to comprehensibly capture biological processes that are modulated by Mn. We uncovered that Mn scarcity influence diverse biological processes associated with fungal fitness including morphogenetic switch, invasion of host cells and antifungal sensitivity. We also uncovered that Mn levels influence the abundance of iron and zinc emphasizing the complex crosstalk between ions metals. Deletion of SMF12, a member of Mn Nramp transporters confirmed its contribution to Mn uptake. In accordance with the RNA-seq data, smf12 was unable to form hyphae and damage host cells, and exhibited sensitivity to azole antifungals. We also found that unfolded protein response (UPR), likely activated by decreased glycosylation under Mn limitation, was essential to promote C. albicans growth. RNA-seq profiling of cells exposed to Mn excess uncovered that the UPR signaling was also essential to bypass Mn toxicity. Collectively, this study underscores the importance of Mn homeostasis in fungal virulence, and comprehensively provides a transcriptional portrait of biological functions that are modulated by Mn in a fungal pathogen.
2024-02-13 | GSE245114 | GEO
Project description:Escherichia coli possesses >65 small proteins of <50 amino acids, many of which are uncharacterized. We have identified a new small protein, MntS, involved in manganese homeostasis. Manganese is a critical micronutrient, serving as an enzyme cofactor and protecting against oxidative stress. Yet manganese is toxic in excess and little is known about its function in cells. Bacteria carefully control intracellular manganese levels using the transcription regulator MntR. Before this work, mntH, which encodes a manganese importer, was the only gene known to respond to manganese via MntR repression in E. coli K12. We demonstrated that mntS is another member of the MntR manganese regulon. We also identified yebN, which encodes a putative manganese efflux pump, as the first gene positively regulated by MntR in Enterobacteria. Since MntS is expressed when manganese levels are low, causes manganese sensitivity when overexpressed, and binds manganese, we propose that MntS may be a manganese chaperone. This study reveals new factors involved in manganese regulation and metabolism and expands our knowledge of how small proteins function. Two E. coli strains, MG1655 (wild type) and GSO458 (Delta-mntR) were grown to OD600 ~ 0.5 in M9 glucose media at 37 M-BM-:C and treated with 10 microM MnCl2. In the first experiment, this incubation with 10 microM MnCl2 was for 60 min and in the second experiment, it was for 10 min. RNA was extracted using the hot phenol method and cDNA prepared and hybridized according the manufacturer's instructions (Affymetrix).
2011-12-08 | E-GEOD-25318 | biostudies-arrayexpress
Project description:Escherichia coli possesses >65 small proteins of <50 amino acids, many of which are uncharacterized. We have identified a new small protein, MntS, involved in manganese homeostasis. Manganese is a critical micronutrient, serving as an enzyme cofactor and protecting against oxidative stress. Yet manganese is toxic in excess and little is known about its function in cells. Bacteria carefully control intracellular manganese levels using the transcription regulator MntR. Before this work, mntH, which encodes a manganese importer, was the only gene known to respond to manganese via MntR repression in E. coli K12. We demonstrated that mntS is another member of the MntR manganese regulon. We also identified yebN, which encodes a putative manganese efflux pump, as the first gene positively regulated by MntR in Enterobacteria. Since MntS is expressed when manganese levels are low, causes manganese sensitivity when overexpressed, and binds manganese, we propose that MntS may be a manganese chaperone. This study reveals new factors involved in manganese regulation and metabolism and expands our knowledge of how small proteins function.
2011-12-08 | GSE25318 | GEO
Project description:Chitin oligomers, released from fungal cell walls by endochitinase, induce defense and related cellular responses in many plants. However, little is known about chitin responses in the model plant Arabidopsis. We describe here a large scale characterization of gene expression patterns in Arabidopsis in response to chitin treatment using an Arabidopsis microarray consisting of 2,375 EST clones representing putative defense-related and regulatory genes. Transcript levels for 71 ESTs, representing 61 genes, were altered >3-fold in chitin-treated seedlings relative to control seedlings. A number of transcripts exhibited altered accumulation as early as 10 min after exposure to chitin, representing some of the earliest changes in gene expression observed in chitin-treated plants. Included among the 61 genes are those that have been reported to be elicited by various pathogen-related stimuli in other plants. Additional genes, including genes of unknown function, were also identified broadening our understanding of chitin-elicited responses. Among transcripts with enhanced accumulation, one cluster was enriched in genes with both the W-box promoter element and a novel regulatory element. In addition, a number of transcripts had decreased abundance, encoding several proteins involved in cell wall strengthening and wall deposition. The chalcone synthase promoter element was identified in the upstream regions of these genes, suggesting that pathogen signals may suppress expression of some genes. These data indicate that Arabidopsis will be an excellent model to elucidate mechanisms of chitin elicitation in plant defense. Groups of assays that are related as part of a time series. Keywords: time_series_design
2005-09-09 | GSE3273 | GEO