Manganese homeostasis modulates fungal virulence and stress tolerance in Candida albicans
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ABSTRACT:
PROVIDER: PRJNA1026965 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26359136_1.fastq.gz | Fastqsanger.gz | |||
| SRR26359136_2.fastq.gz | Fastqsanger.gz | |||
| SRR26359137_1.fastq.gz | Fastqsanger.gz | |||
| SRR26359137_2.fastq.gz | Fastqsanger.gz | |||
| SRR26359138_1.fastq.gz | Fastqsanger.gz |
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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:Due to the scarcity of transition metals within the human host, fungal pathogens have evolved sophisticated mechanisms to uptake and utilize these micronutrients at the infection interface. While considerable attention was turned to iron and copper acquisition mechanisms and their importance in fungal fitness, less was done regarding either the role of manganese (Mn) in infectious processes or the cellular mechanism by which fungal cells achieve their Mn-homeostasis. Here, we undertook transcriptional profiling in the pathogenic fungus Candida albicans experiencing both Mn starvation and excess to capture biological processes that are modulated by this metal. We uncovered that Mn scarcity influences diverse processes associated with fungal fitness including invasion of host cells and antifungal sensitivity. We show that Mn levels influence the abundance of iron and zinc emphasizing the complex crosstalk between metals. The deletion of SMF12, a member of Mn Nramp transporters, confirmed its contribution to Mn uptake. smf12 was unable to form hyphae and damage host cells and exhibited sensitivity to azoles. We found that the unfolded protein response (UPR), likely activated by decreased glycosylation under Mn limitation, was required to recover growth when cells were shifted from an Mn-starved to an Mn-repleted medium. RNA-seq profiling of cells exposed to Mn excess revealed that UPR was also activated. Furthermore, the UPR signaling axis Ire1-Hac1 was required to bypass Mn toxicity. Collectively, this study underscores the importance of Mn homeostasis in fungal virulence and comprehensively provides a portrait of biological functions that are modulated by Mn in a fungal pathogen.ImportanceTransition metals such as manganese provide considerable functionality across biological systems as they are used as cofactors for many catalytic enzymes. The availability of manganese is very limited inside the human body. Consequently, pathogenic microbes have evolved sophisticated mechanisms to uptake this micronutrient inside the human host to sustain their growth and cause infections. Here, we undertook a comprehensive approach to understand how manganese availability impacts the biology of the prevalent fungal pathogen, Candida albicans. We uncovered that manganese homeostasis in this pathogen modulates different biological processes that are essential for host infection which underscores the value of targeting fungal manganese homeostasis for potential antifungal therapeutics development.
| S-EPMC10964418 | biostudies-literature
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:Transcriptional profiling of SirR and manganese regulated expression of genes in Mycobacterium tuberculosis strains comparing high manganese vs. low manganese in Rv (wild type Mycobacterium tuberculosis) and ST70 (mntR mutant strain of Mycobacterium tuberculosis) Two strains each with two conditions experiment, Rv (Mycobacterium tuberculosis wild type strain) high manganese vs. low manganese and ST70 (mntR mutant strain of Mycobacterium tuberculosis) high manganese vs. low manganese. Number of biological replicates is 3 for each condition for each strain.
2015-12-08 | E-GEOD-70812 | biostudies-arrayexpress
Project description:Inside the human host, the pathogenic yeast Candida albicans colonizes predominantly oxygen-poor niches such as the gastrointestinal and vaginal tracts, but also oxygen-rich environments such as cutaneous epithelial cells and oral mucosa. This suppleness requires an effective mechanism to reprogram reversibly the primary metabolism in response to oxygen variation. Here, we have uncovered that Snf5, a subunit of SWI/SNF chromatin remodeling complex, is a major transcriptional regulator that links oxygen status to the metabolic capacity of C. albicans. Snf5 and other subunits of SWI/SNF complex were required to activate genes of carbon utilization and other carbohydrates related process specifically under hypoxia. snf5 mutant exhibited an altered metabolome reflecting that SWI/SNF plays an essential role in maintaining metabolic homeostasis and carbon flux in C. albicans under hypoxia. Snf5 was necessary to activate the transcriptional program linked to both commensal and invasive growth. Accordingly, snf5 was unable to maintain its growth in the stomach, the cecum and the colon of mice. snf5 was also avirulent as it was unable to invade Galleria larvae or to cause damage to human enterocytes and murine macrophages. Among candidates of signaling pathways in which Snf5 might operate, phenotypic analysis revealed that mutants of Ras1-cAMP-PKA pathway, as well as mutants of Yak1 and Yck2 kinases exhibited a similar carbon flexibility phenotype as did snf5 under hypoxia. Genetic interaction analysis indicated that the adenylate cyclase Cyr1, a key component of the Ras1-cAMP pathway genetically with Snf5. Our study yielded new insight into the oxygen-sensitive regulatory circuit that control metabolic flexibility, stress, commensalism and virulence in C. albicans.
2019-09-19 | GSE137655 | GEO
Project description:Transcriptional profiling of SirR and manganese regulated expression of genes in Mycobacterium tuberculosis strains comparing high manganese vs. low manganese in Rv (wild type Mycobacterium tuberculosis) and ST70 (mntR mutant strain of Mycobacterium tuberculosis)
2015-12-08 | GSE70812 | GEO
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:Transcriptomic analysis of wild type and GCN5-deficient Candida albicans cells prior to and after treatment with Caspofungin 15 min and 45 min was done to determine the transcriptional changes in these strains
2019-07-26 | GSE123412 | GEO
Project description:At human body temperature, the fungal pathogen Candida albicans can transition from yeast to filamentous morphologies in response to host-relevant cues. Additionally, elevated temperatures encountered during febrile episodes can independently induce C. albicans filamentation. However, the underlying genetic pathways governing this developmental transition in response to elevated temperature remain largely unexplored. Here, we conducted a functional genomic screen to unravel the genetic mechanisms orchestrating C. albicans filamentation specifically in response to elevated temperature, implicating 45% of genes associated with the spliceosome or pre-mRNA splicing in this process. Employing RNA-Seq to elucidate the relationship between mRNA splicing and filamentation, we identified greater levels of intron retention in filaments compared to yeast, which correlated with reduced expression of the affected genes. Intriguingly, homozygous deletion of a gene encoding a spliceosome component important for filamentation (PRP19) caused even greater levels of intron retention compared with wild-type and globally dysregulated gene expression. This suggests that intron retention is a mechanism for fine-tuning gene expression during filamentation, with perturbations of the spliceosome exacerbating this process and blocking filamentation. Overall, this study unveils a novel biological process governing C. albicans filamentation, providing new insights into the complex regulation of this key virulence trait.
2024-05-28 | GSE262764 | GEO