1036. Whole Genome Sequencing Analysis of a Large Cohort of Staphylococcus epidermidis Blood Culture Positive Isolates From a Multicenter Clinical Trial
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ABSTRACT:
SUBMITTER: Dib R
PROVIDER: S-EPMC6255067 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Project description:Staphylococcus epidermidis is an important cause of nosocomial infection and bacteremia. It is also a common contaminant of blood cultures and, as a result, there is frequently uncertainty as to its diagnostic significance when recovered in the clinical laboratory. One molecular strategy that might be of value in clarifying the interpretation of S. epidermidis identified in blood culture is multilocus sequence typing. Here, we examined 100 isolates of this species (50 blood isolates representing true bacteremia, 25 likely contaminant isolates, and 25 skin isolates) and the ability of sequence typing to differentiate them. Three machine learning algorithms (classification regression tree, support vector machine, and nearest neighbor) were employed. Genetic variability was substantial between isolates, with 44 sequence types found in 100 isolates. Sequence types 2 and 5 were most commonly identified. However, among the classification algorithms we employed, none were effective, with CART and SVM both yielding only 73% diagnostic accuracy and nearest neighbor analysis yielding only 53% accuracy. Our data mirror previous studies examining the presence or absence of pathogenic genes in that the overlap between truly significant organisms and contaminants appears to prevent the use of MLST in the clarification of blood cultures recovering S. epidermidis.
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Project description:Staphylococcus epidermidis is a common cause of catheter-related bloodstream infections, resulting in significant morbidity and mortality and increased hospital costs. The ability to form biofilms plays a crucial role in pathogenesis; however, not all clinical isolates form biofilms under normal in vitro conditions. Strains containing the ica operon can display significant phenotypic variation with respect to polysaccharide intracellular adhesin (PIA)-based biofilm formation, including the induction of biofilms upon environmental stress. Using a parallel microfluidic approach to investigate flow as an environmental signal for S. epidermidis biofilm formation, we demonstrate that fluid shear alone induces PIA-positive biofilms of certain clinical isolates and influences biofilm structure. These findings suggest an important role of the catheter microenvironment, particularly fluid flow, in the establishment of S. epidermidis infections by PIA-dependent biofilm formation.
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Project description:We document linezolid dependence among 5 highly linezolid-resistant (LRSE) Staphylococcus epidermidis bloodstream isolates that grew substantially faster at 32 µg/mL linezolid presence. These isolates carried the mutations T2504A and C2534T in multiple 23S rRNA copies and 2 mutations leading to relevant amino acid substitutions in L3 protein. Linezolid dependence could account for increasing LRSE emergence.
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Project description:Mastitis caused by Staphylococcus aureus is a worldwide problem in dairy farms, in part because of the pathogenicity of the bacteria, biofilm formation, and mechanisms of antimicrobial resistance that make the disease difficult to diagnose and treat, which is typically done with the use of beta-lactam antibiotics. The aim of the present study was to determine the virulence and resistance factors of S. aureus isolates from subclinical mastitis, blaZ + /mecA - /mecC - , resistant and sensitive to oxacillin. All isolates were classified as CC97 by MLST analysis, a clonal complex well adapted to the mammary gland and although STAU23 and STAU73 were resistant to oxacillin while STAU32 and STAU78 were sensitive, the genomic analysis identified only the blaZ operon corresponding to resistance to beta-lactams. However, the presence of the sdrC gene was revealed exclusively in resistant isolates, an important adhesin in the colonization process that potentiates pathogenicity in S. aureus. In addition, resistance islands (REIs) were identified in these isolates, suggesting more conserved REIs. In the analysis of SNPs throughout the genome, mutations were found in the trmB and smpB genes of the resistant isolates and in the murD and rimM genes of the sensitive isolates. This study highlights the potential benefit of genome-wide characterization tools to identify molecular mechanisms of S. aureus in bovine mastitis.
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Project description:The release of cells from S. epidermidis biofilms formed on medical devices has been associated with the onset of bloodstream infections, resulting in increased morbidity and mortality rates. This has to do, in part, with the difficulty to accurately diagnose S. epidermidis bloodstream infections. S. epidermidis is a ubiquitous commensal of human skin and mucosa and, thus, a positive blood culture does not always represent an infection, possibly being the result of contamination during blood collection. As such, there is a high demand to find markers that can help clinicians to distinguish infection (clinical isolates) from contamination (commensal strains). With that in mind, several studies comparing phenotypic or genetic characteristics of clinical and commensal isolates have been performed over the years. However, because S. epidermidis virulence factors seem to be the same that confer its fitness as a commensal, we hypothesized that the ability of S. epidermidis strains to adapt to the host environment may not depend on a specific phenotypic and/or genetic makeup, but rather on the regulation of gene transcription. Thus, using RNA-Sequencing (RNA-seq), we characterized the transcriptome of commensal and clinical isolates in the context of infection to try to uncover differences and, thus, identify markers that could be used for the diagnostics. Several markers with the potential to discriminate between both groups were highlighted. Nevertheless, when the results obtained were confirmed in a wider collection of clinical and commensal isolates the discriminatory power of the genes initially identified was lost. Although we cannot rule out that the characterization of a larger collection of isolates would identify potential candidates, our transcriptomic data was not able to confirm our initial hypothesis, evidencing S. epidermidis opportunistic nature.
2022-12-09 | GSE179407 | GEO
Project description: Not available
| S-EPMC10969876 | biostudies-literature
Project description:The ability of S. epidermidis to withstand the high bactericidal activity of the host’s blood is crucial for its systemic dissemination. Hence, in order to identify genes and pathways involved in the bacterium’s survival in human blood, we have characterized the transcriptome of S. epidermidis biofilms upon contact with human blood. Our results showed that genes whose transcription was increased in blood included those involved in biosynthesis and metabolism of amino acids, small molecules, carboxylic and organic acids, and cellular ketones. One of the striking changes, observed after 4 hours of exposure to human blood, was the increase in the expression of genes involved in iron utilization, suggesting iron acquisition is an important component of S. epidermidis survival in human blood.
2014-08-29 | GSE52111 | GEO
Project description:We report on an analysis of sequential isolates of Staphylococcus epidermidis from cultures of blood obtained from a patient with acute myeloid leukemia while the patient was receiving linezolid treatment. All 12 isolates had a linezolid MIC of 32 microg/ml. A 420-bp domain V region of the 23S rRNA gene from all isolates was amplified, and their nucleotide sequences were determined. A G2576T mutation was identified in all isolates. It was estimated that 67% of the 23S rRNA genes carried this mutation. This is the first report of the failure of linezolid treatment for Staphylococcus epidermidis bacteremia associated with a G2576T mutation in an immunocompromised patient.
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Project description:Staphylococcus epidermidis has been recently recognized as an emerging nosocomial pathogen. There are concerns over the increasing virulence potential of this commensal due to the capabilities of transferring mobile genetic elements to Staphylococcus aureus through staphylococcal chromosomal cassette (SCCmec) and the closely related arginine catabolic mobile element (ACME) and the copper and mercury resistance island (COMER). The potential pathogenicity of S. epidermidis, particularly from blood stream infections, has been poorly investigated. In this study, 24 S. epidermidis isolated from blood stream infections from Oman were investigated using whole genome sequence analysis. Core genome phylogenetic trees revealed one third of the isolates belong to the multidrug resistance ST-2. Genomic analysis unraveled a common occurrence of SCCmec type IV and ACME element predominantly type I arranged in a composite island. The genetic composition of ACME was highly variable among isolates of same or different STs. The COMER-like island was absent in all of our isolates. Reduced copper susceptibility was observed among isolates of ST-2 and ACME type I, followed by ACME type V. In conclusion, in this work, we identify a prevalent occurrence of highly variable ACME elements in different hospital STs of S. epidermidis in Oman, thus strongly suggesting the hypothesis that ACME types evolved from closely related STs.
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