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Extracellular succinate induces spatially organized biofilm formation in Clostridioides difficile

ABSTRACT: Extracellular succinate induces spatially organized biofilm formation in Clostridioides difficile

PROVIDER: PRJNA924839 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23103515.fastq.gz	Fastqsanger.gz
	SRR23103516.fastq.gz	Fastqsanger.gz
	SRR23103517.fastq.gz	Fastqsanger.gz
	SRR23103518.fastq.gz	Fastqsanger.gz
	SRR23103519.fastq.gz	Fastqsanger.gz

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Extracellular succinate induces spatially organized biofilm formation in Clostridioides difficile

Project description:we report that succinate, a metabolite abundantly produced by the dysbiotic gut microbiota, induces in vitro biofilm formation of C. difficile strains. We characterized the morphology and spatial composition of succinate- induced biofilms, and compared to non-induced or deoxycholate-induced biofilms, biofilms induced by succinate are significantly thicker, structurally more complex, and poorer in proteins and exopolysaccharides (EPS).

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Extracellular succinate induces spatially organized biofilm formation in <i>Clostridioides difficile</i>.

Project description:Clostridioides difficile infection associated to gut microbiome dysbiosis is the leading cause for nosocomial diarrhea. The ability of C. difficile to form biofilms has been progressively linked to its pathogenesis as well as its persistence in the gut. Although C. difficile has been reported to form biofilms in an increasing number of conditions, little is known about how these biofilms are formed in the gut and what factors may trigger their formation. Here we report that succinate, a metabolite abundantly produced by the dysbiotic gut microbiota, induces in vitro biofilm formation of C. difficile strains. We characterized the morphology and spatial composition of succinate-induced biofilms, and compared to non-induced or deoxycholate (DCA) induced biofilms. Biofilms induced by succinate are significantly thicker, structurally more complex, and poorer in proteins and exopolysaccharides (EPS). We then applied transcriptomics and genetics to characterize the early stages of succinate-induced biofilm formation and we showed that succinate-induced biofilm results from major metabolic shifts and cell-wall composition changes. Similar to DCA-induced biofilms, biofilms induced by succinate depend on the presence of a rapidly metabolized sugar. Finally, although succinate can be consumed by the bacteria, we found that the extracellular succinate is in fact responsible for the induction of biofilm formation through complex regulation involving global metabolic regulators and the osmotic stress response. Thus, our work suggests that as a gut signal, succinate may drive biofilm formation and help persistence of C. difficile in the gut, increasing the risk of relapse.

| S-EPMC10192414 | biostudies-literature

RNA-seq of Clostridioides difficile ∆cwp66 mutant against wild-type control

Project description:The experiment intends to reveal the difference in gene expression profiles between the wild-type strain and the ∆cwp66 mutant of Clostridioides difficile. We first constructed the ∆cwp66 mutant, and the phenotypic changes of the ∆cwp66 mutant against the wild-type strain were studied. To further elucidate the mechanism of phenotypic changes of the ∆cwp66 mutant, RNA-sequencing experiments were carried out to reveal the underlying mechanism of phenotypic changes.

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Project description:The intestines house a diverse microbiota that must compete for nutrients to survive, but the specific limiting nutrients that control pathogen colonization are not clearly defined. Clostridioides difficile colonization typically requires prior disruption of the microbiota, suggesting that outcompeting commensals for resources is key in establishing C. difficile infection (CDI). The immune protein calprotectin (CP) is released into the gut lumen during CDI to chelate zinc (Zn) and other essential nutrient metals. Yet, the impact of Zn limitation on C. difficile colonization is unknown. To define C. difficile responses to Zn limitation, we performed RNA sequencing on C. difficile exposed to CP. In media with CP, C. difficile upregulated genes involved in metal homeostasis and amino acid metabolism.

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Project description:Gene expression level of Clostridioides difficile (C. difficile) strain R20291 comparing control C. difficile carring pMTL84151 as vector plasmid with C. difficile conjugated with a pMTL84151-03890 gene. Goal was to determine the effects of 03890 gene conjugation on C. difficile strain R20291 gene expression.

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2023-03-23 | E-MTAB-12660 | biostudies-arrayexpress

Global transcriptome analysis of colonic tissue during Clostridioides difficile infection

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