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The transcriptome of the nosocomial pathogen Enterococcus faecalis V583 reveals adaptive responses to growth in blood.

ABSTRACT: BACKGROUND:Enterococcus faecalis plays a dual role in human ecology, predominantly existing as a commensal in the alimentary canal, but also as an opportunistic pathogen that frequently causes nosocomial infections like bacteremia. A number of virulence factors that contribute to the pathogenic potential of E. faecalis have been established. However, the process in which E. faecalis gains access to the bloodstream and establishes a persistent infection is not well understood. METHODOLOGY/PRINCIPAL FINDINGS:To enhance our understanding of how this commensal bacterium adapts during a bloodstream infection and to examine the interplay between genes we designed an in vitro experiment using genome-wide microarrays to investigate what effects the presence of and growth in blood have on the transcriptome of E. faecalis strain V583. We showed that growth in both 2xYT supplemented with 10% blood and in 100% blood had a great impact on the transcription of many genes in the V583 genome. We identified several immediate changes signifying cellular processes that might contribute to adaptation and growth in blood. These include modulation of membrane fatty acid composition, oxidative and lytic stress protection, acquisition of new available substrates, transport functions including heme/iron transporters and genes associated with virulence in E. faecalis. CONCLUSIONS/SIGNIFICANCE:The results presented here reveal that cultivation of E. faecalis in blood in vitro has a profound impact on its transcriptome, which includes a number of virulence traits. Observed regulation of genes and pathways revealed new insight into physiological features and metabolic capacities which enable E. faecalis to adapt and grow in blood. A number of the regulated genes might potentially be useful candidates for development of new therapeutic approaches for treatment of E. faecalis infections.

SUBMITTER: Vebo HC

PROVIDER: S-EPMC2766626 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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The transcriptome of the nosocomial pathogen Enterococcus faecalis V583 reveals adaptive responses to growth in blood.

Vebø Heidi C HC Snipen Lars L Nes Ingolf F IF Brede Dag A DA

PloS one 20091104 11

<h4>Background</h4>Enterococcus faecalis plays a dual role in human ecology, predominantly existing as a commensal in the alimentary canal, but also as an opportunistic pathogen that frequently causes nosocomial infections like bacteremia. A number of virulence factors that contribute to the pathogenic potential of E. faecalis have been established. However, the process in which E. faecalis gains access to the bloodstream and establishes a persistent infection is not well understood.<h4>Methodol ...[more]

PMID: 19888459

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Project description:Emerging antibiotic resistance among clinically relevant bacteria, paired with their ability to form biofilms on medical and technical devices, represents a serious problem in terms of effective and long-term decontamination in health care environments and gives rise to an urgent need for new antimicrobial materials. Here we present the first study of the impact of AGXXÂ®, a novel broad-spectrum antimicrobial surface coating consisting of micro galvanic elements formed by silver and ruthenium, on the transcriptome of the nosocomial pathogen Enterococcus faecalis. E. faecalis was subjected to metal stress by growing it for different periods of time in the presence of AGXXÂ® or silver-coated steel meshes. Subsequently, total RNA was isolated and next-generation RNA sequencing was performed to analyze variations in gene expression levels in the presence of the antimicrobial materials with focus on known stress genes. Exposure to AGXXÂ® had a large impact on the transcriptome of E. faecalis. After 24 minutes almost 1/5 of the E. faecalis genome displayed differential expression. At each time-point the cop operon was strongly up-regulated, providing indirect evidence for the presence of free Ag+-ions. Moreover, exposure to AGXXÂ® induced a broad general stress response in E. faecalis. Genes coding for the chaperones GroEL and GroES as well as the Clp proteases ClpE and ClpB were among the top up-regulated heat shock genes. Furthermore, differential expression of genes coding for thioredoxin, superoxide dismutase and glutathione synthetase indicates a high level of oxidative stress. We postulate a mechanism of action where the combination of Ag+-ions and reactive oxygen species generated by AGXXÂ® results in a synergistic antimicrobial effect, which is superior to that of conventional silver coatings. Gene expression analysis of Enterococcus faecalis 12030 either subjected to metal stress by exposure to an antimicrobial AGXXÂ®- or Ag-coated V2A steel mesh or exposed to an uncoated V2A steel mesh or left untreated performing RNA Sequencing with an Ion ProtonTM Sequencer and subsequent data analysis with a T-REx RNA-Sequencing expression analysis pipeline.

Dataset Information

The transcriptome of the nosocomial pathogen Enterococcus faecalis V583 reveals adaptive responses to growth in blood.

Publications

The transcriptome of the nosocomial pathogen Enterococcus faecalis V583 reveals adaptive responses to growth in blood.

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