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Differential stress transcriptome landscape of historic and recently emerged hypervirulent strains of Clostridium difficile strains determined using RNA-seq.

ABSTRACT: C. difficile is the most common cause of nosocomial diarrhea in North America and Europe. Genomes of individual strains of C. difficile are highly divergent. To determine how divergent strains respond to environmental changes, the transcriptomes of two historic and two recently isolated hypervirulent strains were analyzed following nutrient shift and osmotic shock. Illumina based RNA-seq was used to sequence these transcriptomes. Our results reveal that although C. difficile strains contain a large number of shared and strain specific genes, the majority of the differentially expressed genes were core genes. We also detected a number of transcriptionally active regions that were not part of the primary genome annotation. Some of these are likely to be small regulatory RNAs.

SUBMITTER: Scaria J

PROVIDER: S-EPMC3820578 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Differential stress transcriptome landscape of historic and recently emerged hypervirulent strains of Clostridium difficile strains determined using RNA-seq.

Scaria Joy J Mao Chunhong C Chen Jenn-Wei JW McDonough Sean P SP Sobral Bruno B Chang Yung-Fu YF

PloS one 20131107 11

C. difficile is the most common cause of nosocomial diarrhea in North America and Europe. Genomes of individual strains of C. difficile are highly divergent. To determine how divergent strains respond to environmental changes, the transcriptomes of two historic and two recently isolated hypervirulent strains were analyzed following nutrient shift and osmotic shock. Illumina based RNA-seq was used to sequence these transcriptomes. Our results reveal that although C. difficile strains contain a la ...[more]

PMID: 24244315

Similar Datasets

Differential stress transcriptome landscape of historic and recently emerged hypervirulent strains of Clostridium difficile strains determined using RNA-seq

Project description:Purpose: To determine how divergent strains of C. difficile respond to environmental changes, the transcriptomes of two historic and two recently isolated hypervirulent strains were analyzed following nutrient shift and osmotic shock. Methods: Following nutrient shift and osmotic shock, mRNA profile were determined using sequing of transcriptome in biological duplicates, using Illumina Hi-seq 2000. Results: After applying the quality control steps, for each sample, sequence reads were 90 nucleotides in length and the total number of reads per sample was ~ 26.6 million on average. Expression of more than 90% CDS was detected under the three experimental conditions combined. About 20% of these genes were indentified to be differentially expressed at 1.5 fold or more. Conclusions: Our results reveal that although C. difficile strains contain a large number of shared and strain specific genes, the majority of the differentially expressed genes were core genes. We also detected a number of transcriptionally active regions that were not part of the primary genome annotation. Some of these are likely to be small regulatory RNAs.

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Differential stress transcriptome landscape of historic and recently emerged hypervirulent strains of Clostridium difficile strains determined using RNA-seq

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Project description:Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. By broth microdilution techniques, we determined the MIC values of the anthelmintics against 16 C. difficile isolates of defined PCR-ribotype. The anthelmintics broadly inhibited C. difficile growth in vitro via a membrane depolarization mechanism. Interestingly, the salicylanilides were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. The salicylanilides were poorly active against select gut commensals (Bacteroides, Bifidobacterium and Lactobacillus species), and were non-hemolytic and non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable properties for repositioning as anti-C. difficile agents.

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Project description:In the present study we conducted a gene-wide analysis from nine couples of C. difficile strains. Each couple is composed of a high potential virulence (HPV) strain associated with its control (CON) strain. The HPV strains were chosen using two clinical criteria: prevalence and severity. The prevalent strains, defined in this study by an overrepresentation in European hospital, were associated with phylogenetically close control strain but rarely found in hospital. In other hand, the severe strains sampled on patient with very serious symptoms were associated with phylogenetically identical strain but that gave mild symptoms in another patient. The aim of this work was to determined if we could explain at least a part of the clinical criteria differences between these nine couples of strains in the light of their genomic and transcriptomic differences.

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