Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA

ABSTRACT: Fungal pathogens threaten ecosystems and human health. Understanding the molecular basis of their virulence is key to develop new treatment strategies. Here, we characterize NCS2*, a point mutation identified in a clinical baker's yeast isolate. Ncs2 is essential for 2-thiolation of tRNA and the NCS2* mutation leads to increased thiolation at body temperature. NCS2* yeast exhibits enhanced fitness when grown at elevated temperatures or when exposed to oxidative stress, inhibition of nutrient signalling, and cell-wall stress. Importantly, Ncs2* alters the interaction and stability of the thiolase complex likely mediated by nucleotide binding. The absence of 2-thiolation abrogates the in vivo virulence of pathogenic baker's yeast in infected mice. Finally, hypomodification triggers changes in colony morphology and hyphae formation in the common commensal pathogen Candida albicans resulting in decreased virulence in a human cell culture model. These findings demonstrate that 2-thiolation of tRNA acts as a key mediator of fungal virulence and reveal new mechanistic insights into the function of the highly conserved tRNA-thiolase complex.

ORGANISM(S): Candida albicans

PROVIDER: GSE199422 | GEO | 2023/09/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The thiolation modification of tRNA is essential for plant immunity

Project description:Plants have evolved sophisticated mechanisms to regulate gene expression to activate immune responses against pathogen infections. However, how the translation system contributes to plant immunity is largely unknown. The evolutionarily conserved thiolation modification of tRNA ensures efficient decoding during translation. Here we show that tRNA thiolation is required for plant immunity in Arabidopsis. The Arabidopsis cgb mutant is hyper-susceptible to the pathogen Pseudomonas syringae. CGB encodes ROL5, a homolog of yeast NCS6 required for tRNA thiolation. ROL5 physically interacts with CTU2, a homolog of yeast NCS2. Mutations in either ROL5 or CTU2 result in loss of tRNA thiolation. Further analyses reveal that tRNA thiolation is required for both transcriptional reprogramming and translational reprogramming during immune responses. The translation efficiency of immune-related proteins reduces when tRNA thiolation is absent. Our study not only uncovers a new biological function of tRNA thiolation but also reveals a new mechanism for plant immunity.

2022-08-31 | GSE183087 | GEO

The thiolation modification of tRNA is essential for plant immunity

2022-07-05 | PXD028189 |

Time course gene expression profile of YPD medium grown Candida albicans mss11 mutant

Project description:Candida albicans is an important fungal pathogen in humans. Several virulence factors of C. albicans have been reported, including a morphological transition from yeast to filamentous forms (hyphae and pseudohyphae). Mss11 is a transcriptional activator required for hyphal formation. To reveal the potential target genes of Mss11, DNA microarray analysis was performed to compare wild type and mss11-deleted mutant.

2016-09-24 | GSE51168 | GEO

A highly conserved tRNA modification contributes to C. albicans filamentation and virulence

Project description:tRNA modifications play important roles in maintaining translation accuracy in all domains of life. Disruptions in the tRNA modification machinery, especially of the anticodon stem loop, can be lethal for many bacteria and lead to a broad range of phenotypes in baker’s yeast. Very little is known about the function of tRNA modifications in host-pathogen interactions, where rapidly changing environments and stresses require fast adaptations. We found that two closely related fungal pathogens of humans, the highly pathogenic Candida albicans and its much less pathogenic sister species, Candida dubliniensis, differ in the function of a tRNA-modifying enzyme. This enzyme, Hma1, exhibits speciesspecific effects on the ability of the two fungi to grow in the hypha morphology, which is central to their virulence potential. We show that Hma1 has tRNA-threonylcarbamoyladenosine dehydratase activity, and its deletion alters ribosome occupancy, especially at 37°C—the body temperature of the human host. A C. albicans HMA1 deletion mutant also shows defects in adhesion to and invasion into human epithelial cells and shows reduced virulence in a fungal infection model. This links tRNA modifications to host-induced filamentation and virulence of one of the most important fungal pathogens of humans.

2024-04-04 | GSE199421 | GEO

Global transcriptome of Sclerotinia sclerotiorum during in vitro growth and Arabidopsis thaliana infection

Project description:Cooperation is associated with major transitions in evolution such as the emergence of multicellularity. It is central to the evolution of many complex traits in nature, including growth and virulence in pathogenic bacteria. Whether cells of multicellular parasites function cooperatively during infection remains however largely unknown. Here, we show that hyphal cells of the fungal pathogen Sclerotinia sclerotiorum reprogram towards division of labor to facilitate the colonization of host plants. Using global transcriptome sequencing, we reveal that gene expression patterns diverge markedly in cells at the center and apex of hyphae during A. thaliana colonization compared to in vitro growth. We reconstructed a genome-scale metabolic model for S. sclerotiorum and used flux balance analysis to demonstrate metabolic heterogeneity supporting division of labor between hyphal cells. Accordingly, continuity between the central and apical compartments of invasive hyphae was required for optimal growth in planta. Using a multi-cell model of fungal hyphae, we show that this cooperative functioning enhances fungal growth predominantly during host colonization. Our work identifies cooperation in fungal hyphae as a mechanism emerging at the multicellular level to support host colonization and virulence.

2019-01-24 | GSE116194 | GEO

Screens of C. albicans deletion collections in the murine reveals role for filamentation transcription factors

Project description:Candida albicans is a human gut commensal and an opportunistic pathogen. The ability to transition from yeasts to invasive hyphae is a central virulence attribute, but it is unclear how these two cell types function during commensal growth. Using FISH to visualize C. albicans in a murine gut colonization model, we observed the co-occurrence of yeasts and hyphae throughout the gastrointestinal tract. Forward genetic analysis revealed that major transcriptional activators of yeast-to-hypha morphogenesis have unexpected activity as potent inhibitors of commensalism. In vivo FISH, transcriptomic, and genetic analyses indicate that the morphogenesis program inhibits commensal fitness, not through control of cell shape as expected from in vitro studies, but by activating expression of a hypha-specific pro-inflammatory secreted protease and a hyphal cell surface adhesin. These results reveal a tradeoff between fungal programs supporting commensalism and virulence within the commensal niche in which selection against hypha-specific markers limits the disease-causing potential of this ubiquitous commensal-pathogen.

2018-12-31 | GSE124139 | GEO

High throughput RNA sequencing of C. albicans colonizing the murine GI tract reveals a role for a secreted effecter in commensalism

2018-12-31 | GSE124137 | GEO

RNA-Seq analysis of WT and BbWor1 disruption strain in beauveria bassiana

Project description:Wor1 is a conserved fungal regulatory protein that control the phenotypic switching and pathogenicity of Candida albicans.We simulated three models of Beauveria bassiana morphological transitions, including CTH (conidia to hyphae), HTC (hyphae to conidia) and BTB (blastospore to blastospore).We find that disruption of BbWor1 (an ortholog of Wor1) resulted in a distinct reduction in the time required for germination (CTH), a significant increase in hyphal growth and a decrease in the yield of conidia (HTC), indicating that BbWor1 positively controls conidia production and negatively regulates hyphal growth in conidia-hyphae switching. Meanwhile, the ΔBbWor1 prominently decreased blastospore yield, as well as shortening G0/G1 phase and prolonging G2/M phase, under the BTB model. Importantly, BbWor1 contributed to conidia-hyphae switching and blastospore propagation via different genetic pathways, and yeast one-hybrid testing demonstrated the necessity of BbWor1 to control the transcription of an allergen-like protein gene (BBA_02580), as well as a conidial wall protein gene (BBA_09998). Moreover, the dramatically weakened virulence of ΔBbWor1 was examined by immersion and injection methods.

2021-07-03 | GSE178974 | GEO

Lack of TRMT2A, a tRNA methyltransferase, induces the generation of tRNA-derived small RNAs due to m5U54 tRNA hypomodification [Array]

Project description:Transfer RNA (tRNA) molecules contain a variety of post-transcriptional modifications which are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation, to gene expression control and cellular stress response. Recent evidence show that tsRNAs are also modified, however the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. This modification is catalyzed by the tRNA methyltransferase TRMT2A, but its biological role remains largely unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

2021-04-20 | GSE164168 | GEO