Alterations in GyrA and ParC Associated with Fluoroquinolone Resistance in
            <i>Enterococcus faecium</i>

Amin, Nagwa El; Jalal, Shah; Wretlind, Bengt

doi:10.1128/aac.43.4.947

Cited by 62 publications

(36 citation statements)

References 30 publications

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“…Two mutation events in each gene were found (Table 1), and both aa combinations (GyrA Arg83, ParC Ile80 or GyrA Ile83, ParC Arg80) have been described previously in E. faecium isolates with ciprofloxacin MICs ≥16 mg/L [25], [40], [41]. Moreover, the tetracycline resistance determinant tetM and the macrolide resistance determinant ermB were also found in three and four WGS isolates, respectively (Table S2).…”

Section: Resultssupporting

confidence: 52%

A Multicentre Hospital Outbreak in Sweden Caused by Introduction of a vanB2 Transposon into a Stably Maintained pRUM-Plasmid in an Enterococcus faecium ST192 Clone

et al. 2014

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The clonal dissemination of VanB-type vancomycin-resistant Enterococcus faecium (VREfm) strains in three Swedish hospitals between 2007 and 2011 prompted further analysis to reveal the possible origin and molecular characteristics of the outbreak strain. A representative subset of VREfm isolates (n = 18) and vancomycin-susceptible E. faecium (VSEfm, n = 2) reflecting the spread in time and location was approached by an array of methods including: selective whole genome sequencing (WGS; n = 3), multi locus sequence typing (MLST), antimicrobial susceptibility testing, virulence gene profiling, identification of mobile genetic elements conferring glycopeptide resistance and their ability to support glycopeptide resistance transfer. In addition, a single VREfm strain with an unrelated PFGE pattern collected prior to the outbreak was examined by WGS. MLST revealed a predominance of ST192, belonging to a hospital adapted high-risk lineage harbouring several known virulence determinants (n≥10). The VREfm outbreak strain was resistant to ampicillin, gentamicin, ciprofloxacin and vancomycin, and susceptible to teicoplanin. Consistently, a vanB2-subtype as part of Tn1549/Tn5382 with a unique genetic signature was identified in the VREfm outbreak strains. Moreover, Southern blot hybridisation analyses of PFGE separated S1 nuclease-restricted total DNAs and filter mating experiments showed that vanB2-Tn1549/Tn5382 was located in a 70-kb sized rep 17/pRUM plasmid readily transferable between E. faecium. This plasmid contained an axe-txe toxin-antitoxin module associated with stable maintenance. The two clonally related VSEfm harboured a 40 kb rep 17/pRUM plasmid absent of the 30 kb vanB2-Tn1549/Tn5382 gene complex. Otherwise, these two isolates were similar to the VREfm outbreak strain in virulence- and resistance profile. In conclusion, our observations support that the origin of the multicentre outbreak was caused by an introduction of vanB2-Tn1549/Tn5382 into a rep 17/pRUM plasmid harboured in a pre-existing high-risk E. faecium ST192 clone. The subsequent dissemination of VREfm to other centres was primarily caused by clonal spread rather than plasmid transfer to pre-existing high-risk clones.

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Section: Resultssupporting

confidence: 52%

A Multicentre Hospital Outbreak in Sweden Caused by Introduction of a vanB2 Transposon into a Stably Maintained pRUM-Plasmid in an Enterococcus faecium ST192 Clone

et al. 2014

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“…This indicates alternative resistance mechanisms or upregulation and downregulation of genes other than those investigated here but involved in higher expression of fluoroquinolone non-susceptibility, such as efflux pumps or topoisomerase protection genes [36,[43][44][45]. Several authors have also reported double mutations in parC and gyrA prevalent among high-level ciprofloxacin-resistant clinical isolates of E. faecium [19,20,34], whereas other reports demonstrated single parC mutations as sufficient to confer elevated ciprofloxacin MICs in natural isolates [17,33]. In some of the previous studies, sequential mutations were introduced by challenging test strains with growing concentrations of fluoroquinolones in vitro [36,37].…”

Section: Discussionmentioning

confidence: 81%

“…However, the respective strain collections were mostly limited or restricted in terms of time, geographical coverage or any homogeneity, thus not allowing any specific epidemiological conclusions [20,33,34]. Here, based on a comprehensive collection of clinical E. faecium isolated from German hospital patients between 1997 and 2007, we showed a permanent increase in their MICs for ciprofloxacin (Table 1).…”

Section: Discussionmentioning

confidence: 84%

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High-level ciprofloxacin resistance among hospital-adapted Enterococcus faecium (CC17)

Werner

Fleige

Ewert

et al. 2010

International Journal of Antimicrobial Agents

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Hospital-adapted Enterococcus faecium differ from their colonising variants in humans and animals by additional genomic content. Molecular typing based on multilocus sequence typing (MLST) allows allocation of isolates to specific clonal complexes (CCs), such as CC17 for hospital-adapted strains. Acquired ampicillin resistance is a specific feature of these hospital isolates, especially in Europe. A few recent reports have described acquired high-level ciprofloxacin resistance as a supposed feature of hospital-adapted E. faecium strains. In the present retrospective analysis, ciprofloxacin minimum inhibitory concentrations (MICs) of 609 clinical isolates from German hospital patients (1997-2007) were determined and a breakpoint for high-level resistance was deduced (>16mg/L). Acquired high-level ciprofloxacin resistance was distributed among isolates of 26 different MLST types (all CC17), indicating a wide prevalence of this acquired resistance trait among the hospital-adapted E. faecium population. High-level ciprofloxacin resistance was linked to gyrA and parC mutations in 98 investigated isolates. Eleven different allele types or combinations thereof were identified. Their allocation to specific MLST and pulsed-field gel electrophoresis (PFGE) types revealed differences in the emergence and spread of corresponding mutations and strains.

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“…Our data revealed a high transfer rate (10 −4 –10 −5 ) for both, tetracycline and doxycycline resistance traits, indicating potential involvement of Tn 916 . Ampicillin and enrofloxacin resistance traits could not be transferred in vitro , possibly because the conferring resistance genes such as pbp5 or gyrA are commonly encoded on non-transferable regions of the chromosome [72], [73].…”

Section: Discussionmentioning

confidence: 99%

Dogs Leaving the ICU Carry a Very Large Multi-Drug Resistant Enterococcal Population with Capacity for Biofilm Formation and Horizontal Gene Transfer

Ghosh

Dowd²,

Zurek

2011

PLoS ONE

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The enterococcal community from feces of seven dogs treated with antibiotics for 2–9 days in the veterinary intensive care unit (ICU) was characterized. Both, culture-based approach and culture-independent 16S rDNA amplicon 454 pyrosequencing, revealed an abnormally large enterococcal community: 1.4±0.8×108 CFU gram−1 of feces and 48.9±11.5% of the total 16,228 sequences, respectively. The diversity of the overall microbial community was very low which likely reflects a high selective antibiotic pressure. The enterococcal diversity based on 210 isolates was also low as represented by Enterococcus faecium (54.6%) and Enterococcus faecalis (45.4%). E. faecium was frequently resistant to enrofloxacin (97.3%), ampicillin (96.5%), tetracycline (84.1%), doxycycline (60.2%), erythromycin (53.1%), gentamicin (48.7%), streptomycin (42.5%), and nitrofurantoin (26.5%). In E. faecalis, resistance was common to tetracycline (59.6%), erythromycin (56.4%), doxycycline (53.2%), and enrofloxacin (31.9%). No resistance was detected to vancomycin, tigecycline, linezolid, and quinupristin/dalfopristin in either species. Many isolates carried virulence traits including gelatinase, aggregation substance, cytolysin, and enterococcal surface protein. All E. faecalis strains were biofilm formers in vitro and this phenotype correlated with the presence of gelE and/or esp. In vitro intra-species conjugation assays demonstrated that E. faecium were capable of transferring tetracycline, doxycycline, streptomycin, gentamicin, and erythromycin resistance traits to human clinical strains. Multi-locus variable number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE) of E. faecium strains showed very low genotypic diversity. Interestingly, three E. faecium clones were shared among four dogs suggesting their nosocomial origin. Furthermore, multi-locus sequence typing (MLST) of nine representative MLVA types revealed that six sequence types (STs) originating from five dogs were identical or closely related to STs of human clinical isolates and isolates from hospital outbreaks. It is recommended to restrict close physical contact between pets released from the ICU and their owners to avoid potential health risks.

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Alterations in GyrA and ParC Associated with Fluoroquinolone Resistance in Enterococcus faecium

Cited by 62 publications

References 30 publications

A Multicentre Hospital Outbreak in Sweden Caused by Introduction of a vanB2 Transposon into a Stably Maintained pRUM-Plasmid in an Enterococcus faecium ST192 Clone

A Multicentre Hospital Outbreak in Sweden Caused by Introduction of a vanB2 Transposon into a Stably Maintained pRUM-Plasmid in an Enterococcus faecium ST192 Clone

High-level ciprofloxacin resistance among hospital-adapted Enterococcus faecium (CC17)

Dogs Leaving the ICU Carry a Very Large Multi-Drug Resistant Enterococcal Population with Capacity for Biofilm Formation and Horizontal Gene Transfer

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