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Mechanisms of linezolid resistance among coagulase-negative staphylococci determined by whole-genome sequencing.

ABSTRACT: UNLABELLED:Linezolid resistance is uncommon among staphylococci, but approximately 2% of clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit resistance to linezolid (MIC, ?8 µg/ml). We performed whole-genome sequencing (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28 linezolid-resistant CoNS (21 Staphylococcus epidermidis isolates and 7 Staphylococcus haemolyticus isolates) obtained from blood cultures at a large teaching health system in California between 2007 and 2012. The following well-characterized mutations associated with linezolid resistance were identified in the 23S rRNA: G2576U, G2447U, and U2504A, along with the mutation C2534U. Mutations in the L3 and L4 riboproteins, at sites previously associated with linezolid resistance, were also identified in 20 isolates. The majority of isolates harbored more than one mutation in the 23S rRNA and L3 and L4 genes. In addition, the cfr methylase gene was found in almost half (48%) of S. epidermidis isolates. cfr had been only rarely identified in staphylococci in the United States prior to this study. Isolates of the same sequence type were identified with unique mutations associated with linezolid resistance, suggesting independent acquisition of linezolid resistance in each isolate. IMPORTANCE:Linezolid is one of a limited number of antimicrobials available to treat drug-resistant Gram-positive bacteria, but resistance has begun to emerge. We evaluated the genomes of 28 linezolid-resistant staphylococci isolated from patients. Multiple mutations in the rRNA and associated proteins previously associated with linezolid resistance were found in the isolates investigated, underscoring the multifocal nature of resistance to linezolid in Staphylococcus. Importantly, almost half the S. epidermidis isolates studied harbored a plasmid-borne cfr RNA methylase gene, suggesting that the incidence of cfr may be higher in the United States than previously documented. This finding has important implications for infection control practices in the United States. Further, cfr is commonly detected in bacteria isolated from livestock, where the use of phenicols, lincosamides, and pleuromutilins in veterinary medicine may provide selective pressure and lead to maintenance of this gene in animal bacteria.

SUBMITTER: Tewhey R

PROVIDER: S-EPMC4030478 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Mechanisms of linezolid resistance among coagulase-negative staphylococci determined by whole-genome sequencing.

Tewhey Ryan R Gu Bing B Kelesidis Theodoros T Charlton Carmen C Bobenchik April A Hindler Janet J Schork Nicholas J NJ Humphries Romney M RM

mBio 20140513 3

<h4>Unlabelled</h4>Linezolid resistance is uncommon among staphylococci, but approximately 2% of clinical isolates of coagulase-negative staphylococci (CoNS) may exhibit resistance to linezolid (MIC, ≥8 µg/ml). We performed whole-genome sequencing (WGS) to characterize the resistance mechanisms and genetic backgrounds of 28 linezolid-resistant CoNS (21 Staphylococcus epidermidis isolates and 7 Staphylococcus haemolyticus isolates) obtained from blood cultures at a large teaching health system in ...[more]

PMID: 24915435

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Project description:Purpose: The aim of the study was to compare the miRNA expression in non-infected (H) mammary gland parenchyma samples with that of glands infected with coagulase-positive staphy lococci (CoPS) or coagulase-negative staphylococci (CoNS) using next-generation sequencing. Methods: miRNA-seq analysis was performed on mammary gland parenchyma samples collected from non-infected cows and those infected with coagulase-positive or -negative staphylococci. The miRNA libraries were constructed from total RNA using NEBNext Multiplex Small RNA Library Prep Set for Illumina (New England Biolabs) according to the manufacturer protocol. The quantification of the obtained libraries was performed on a Qubit 2.0 spectrophotometer (Invitrogen, Life Technologies), while a quality control on a TapeStation 2200 instrument (D1000 ScreenTape; Agilent). Single-end cycle sequencing was performed on the HiScanSQ platform (Illumina) with the use of TruSeq SR Cluster Kit v3- CBOT-HS and TruSeq SBS Kit v 3 - HS (Illumina). MicroRNA differentially expressed between investigated groups were identified with the DESeq2 software. Results: Comparing the CoPS and H groups, 256 known and 260 potentially new miRNAs were identifed, including 32 that were diferentially expressed (p≤0.05), of which 27 were upregulated and 5 downregulated. Comparing the CoNS and H groups, 242 known and 171 new unique miRNAs were identifed: 10 were upregulated (p≤0.05), and 2 downregulated (p≤0.05). Comparing CoPS with H and CoNS with H, 5 Kyoto Encyclopedia of Genes and Genomes pathways were identifed; in both comparisons, diferentially-expressed miRNAs were associated with the bacterial invasion of epithelial cells and focal adhesion pathways. Four gene ontology terms were identifed in each comparison, with 2 being common to both immune system processes and signal transduction. Conclusions: Obtained results enabled us to characterize the miRNA profile of the mammary gland parenchyma tissue, not only the healthy one but also the tissue infected with coagulase-positive and negative staphylococci as well as allowed identification of miRNAs differing the examined groups and characteristic for the staphylococci infection. They also indicated that miRNAs, especially miR-99 and miR-182, play an essential role in the epigenetic regulation of a range of cellular processes, including immunological systems bacterial growth in dendritic cells and disease pathogenesis (miR-99), DNA repair and tumor progression (miR-182).

Dataset Information

Mechanisms of linezolid resistance among coagulase-negative staphylococci determined by whole-genome sequencing.

Publications

Mechanisms of linezolid resistance among coagulase-negative staphylococci determined by whole-genome sequencing.

Similar Datasets

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