Emergence and dissemination of a linezolid-resistant<i>Staphylococcus capitis</i>clone in Europe

Butin, Marine; Martins-Simões, Patrícia; Pichon, Bruno; Leyssene, D.; Bordes-Couecou, S.; Meugnier, H.; Rouard, Caroline; Lemaître, Nadine; Schramm, Frédéric; Kearns, Angela; Spiliopoulou, Iris; Hyyryläinen, Hanne‐Leena; Dumitrescu, Oana; Vandenesch, François; Dupieux, Céline; Laurent, François

doi:10.1093/jac/dkw516

Cited by 17 publications

(19 citation statements)

References 25 publications

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“…In 2016, Butin et al [17] compared 11 LZR S. capitis with known genome sequences of strains stored in GenBank. All 11 LZR S. capitis strains clustered as a single independent clade, confirming that they belong to a clonal population.…”

Section: Discussionmentioning

confidence: 99%

“…A portion of the extracted genome was subjected to WGS using Illumina technology (HiSeq). Phylogenetic trees were inferred from the WGS data as previously described by Butin et al [17], with some modifications. Briefly, sequences were compared with the seven publicly available S. capitis genomes: CR01 (LN866849), SK14 (ACFR00000000.1), VCU116(AFTX00000000.1), QN1(AJTH00000000.1), AYP1020 (CP007601), C87 (ACRH00000000.1) and LNZR-1 (JGYJ00000000.1).…”

Section: Whole-genome Sequencing (Wgs)mentioning

confidence: 99%

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The epidemiology and molecular characteristics of linezolid-resistant Staphylococcus capitis in Huashan Hospital, Shanghai

Pei

Yang

Lin

et al. 2020

Journal of Medical Microbiology

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Introduction. Linezolid-resistant (LZR) Staphylococcus capitis has recently emerged in our hospital, and its potential resistance mechanisms are still not clear. Aim. This study aimed to investigate the epidemiology, clinical and genetic characteristics, resistance mechanisms and biofilm formation capacity of LZR S. capiti s isolated from patients at Huashan Hospital, Shanghai, PR China between 2012 and 2018. Methodology. Strains were subjected to antimicrobial susceptibility testing (AST) with antibiotics using the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The presence of cfr, optrA and poxtA, as well as mutations in the 23S ribosomal (r)RNA and ribosomal proteins, was investigated using PCR and sequencing techniques. The genetic relationship between isolates was analysed using pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). Biofilm biomasses were detected by using crystal violet staining. Results. Twenty-one LZR S. capitis strains displayed MICs of 32–512 μg ml−1. All LZR strains showed G2576T and C2104T mutations in the 23S rRNA V region. Besides G2576T and C2104T, no base mutations were detected in the V region. The cfr was detected in 12 strains, while optrA and poxtA were not amplified in 21 S . capitis strains. PFGE showed that the LZR S. capitis strains belonged to a single clone. The phylogenetic tree showed that 20 LZR S. capitis strains were highly similar to LNZR-1, isolated from Harbin (located in the north of China) in 2013, which showed resistance to linezolid. Conclusions. In this research, cfr-negative strains displayed linezolid MICs of 32 μg ml−1. In comparison, cfr-positive strains exhibited linezolid MICs of 128–512 μg ml−1, indicating that high levels of linezolid resistance appear to be related to the presence of cfr. The outbreak of LZR S. capitis in our hospital needs to be monitored closely.

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Section: Discussionmentioning

confidence: 99%

Section: Whole-genome Sequencing (Wgs)mentioning

confidence: 99%

The epidemiology and molecular characteristics of linezolid-resistant Staphylococcus capitis in Huashan Hospital, Shanghai

Pei

Yang

Lin

et al. 2020

Journal of Medical Microbiology

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“…Recently, this gene has also been detected in clinical isolates of Enterococcus spp. from North America and Europe ( Brenciani et al, 2016 ; Flamm et al, 2016 ; Cavaco et al, 2017 ; Gawryszewska et al, 2017 ; Pfaller et al, 2017 ), as well as in staphylococci ( Li et al, 2016 ; Butin et al, 2017 ). Phylogenetic analysis has suggested that OptrA belongs to the ABC-F protein subfamily, which is widespread in Gram-positive bacteria ( Murina et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance

et al. 2018

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Despite increasing reports of low-level linezolid-resistant enterococci worldwide, the mechanism of this resistance remains poorly understood. Previous transcriptome studies of low-level linezolid-resistant Enterococcus faecalis isolates have demonstrated a number of significantly up-regulated genes potentially involved in mediation of drug resistance. However, whether the transcriptome faithfully reflects the proteome remains unknown. In this study, we performed quantitative proteomics analysis of membrane proteins in an E. faecalis isolate (P10748) with low-level linezolid-resistance in comparison with two linezolid-susceptible strains 3138 and ATCC 29212, all of which have been previously investigated by whole transcriptome analysis. A total of 8,197 peptides associated with 1,170 proteins were identified in all three isolates with false discovery rate (FDR) at 1% and P < 0.05. There were 14 significantly up-regulated and 6 significantly down-regulated proteins in strain P10748 compared to strains 3138 and ATCC 29212, which were in general positively correlated with transcription levels revealed in previous transcriptome studies. Our analysis suggests that the low-level linezolid-resistance in E. faecalis is conferred primarily by the ATP-binding cassette protein OptrA through ribosomal protection and, possibly, also by the enterococcal surface protein (Esp) and other proteins through biofilm formation. The genetic transfer of optrA is potentially regulated by the surface exclusion protein Sea1, conjugal transfer protein TraB, replication protein RepA and XRE family transcription regulator protein. This report represents the first investigation of the mechanisms of linezolid-resistance in E. faecalis by a quantitative proteomics approach.

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“…S. capitis infection has been observed in neonates and adults with infective endocarditis or bone infections and has historically been viewed as susceptible to a broad range of antibiotics [ 1 ]. However, data have suggested the emergence of multidrug-resistant S. capitis in hospitals across Europe [ 23 ]. A recent study also identified S. capitis as a likely causative agent in nosocomial prosthetic joint infections, with multidrug-resistant S. capitis detected in approximately 28% of isolates [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative activity of ceftobiprole against coagulase-negative staphylococci from the BSAC Bacteraemia Surveillance Programme, 2013–2015

Henriksen

Smart

Hamed

2018

Eur J Clin Microbiol Infect Dis

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Coagulase-negative staphylococci (CoNS) are a significant cause of bacteraemia, the treatment of which is becoming increasingly complex due to the emergence of multidrug-resistant strains. This study aimed to evaluate the in vitro activity of ceftobiprole, an advanced-generation cephalosporin, as compared with other antimicrobial agents against CoNS from patients with bacteraemia. As part of the British Society for Antimicrobial Chemotherapy (BSAC) Bacteraemia Surveillance Programme, 650 blood isolates of CoNS were obtained from patients with bacteraemia at 74 centres throughout the UK and Ireland for the years 2013–2015. Minimum inhibitory concentrations (MICs) of ceftobiprole and other antimicrobial agents were determined using the BSAC agar dilution method. Susceptibility was assessed by European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The majority of the isolates (63.2%) were Staphylococcus epidermidis. Overall, methicillin resistance, as determined by oxacillin susceptibility testing, was observed in 64.2% of isolates. The MIC50/90 of ceftobiprole was 1/2 mg/L, and 100% of CoNS isolates were inhibited at the EUCAST ceftobiprole non-species-specific pharmacokinetic/pharmacodynamic breakpoint of 4 mg/L. Only one isolate was resistant to vancomycin. Overall rates of resistance to ciprofloxacin, clindamycin, erythromycin and teicoplanin were 50.5, 25.1, 68.2 and 20.9%, respectively. In S. epidermidis, resistance to oxacillin was associated with increased resistance to other antimicrobials. Ceftobiprole demonstrated in vitro activity against all CoNS species isolated from patients with bacteraemia and was active against species resistant to other antistaphylococcal antimicrobials. The collection of clinical data regarding the efficacy of ceftobiprole in treating CoNS bacteraemia is warranted.

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Emergence and dissemination of a linezolid-resistantStaphylococcus capitisclone in Europe

Cited by 17 publications

References 25 publications

The epidemiology and molecular characteristics of linezolid-resistant Staphylococcus capitis in Huashan Hospital, Shanghai

The epidemiology and molecular characteristics of linezolid-resistant Staphylococcus capitis in Huashan Hospital, Shanghai

Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis With Low-Level Linezolid-Resistance

Comparative activity of ceftobiprole against coagulase-negative staphylococci from the BSAC Bacteraemia Surveillance Programme, 2013–2015

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