Deletions in a ribosomal protein-coding gene are associated with tigecycline resistance in Enterococcus faecium

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Deletions in a ribosomal protein-coding gene are associated with tigecycline resistance in Enterococcus faecium. / Niebel, Marc; Quick, Joshua; Prieto, Ana Maria Guzman; Hill, Robert L R; Pike, Rachel; Huber, Damon; David, Miruna; Hornsey, Michael; Wareham, David; Oppenheim, Beryl; Woodford, Neil; van Schaik, Willem; Loman, Nicholas.

In: International Journal of Antimicrobial Agents, 20.08.2015.

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Niebel, Marc ; Quick, Joshua ; Prieto, Ana Maria Guzman ; Hill, Robert L R ; Pike, Rachel ; Huber, Damon ; David, Miruna ; Hornsey, Michael ; Wareham, David ; Oppenheim, Beryl ; Woodford, Neil ; van Schaik, Willem ; Loman, Nicholas. / Deletions in a ribosomal protein-coding gene are associated with tigecycline resistance in Enterococcus faecium. In: International Journal of Antimicrobial Agents. 2015.

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@article{3d241202fce746e99ad8404ba73e95a4,
title = "Deletions in a ribosomal protein-coding gene are associated with tigecycline resistance in Enterococcus faecium",
abstract = "Enterococcus faecium is an emerging nosocomial pathogen associated with antibiotic therapy in the hospital environment. Whole-genome sequences were determined for three pairs of related, consecutively collected E. faecium clinical isolates to determine putative mechanisms of resistance to tigecycline. The first isolates (1S, 2S and 3S) in each of the three pairs were sensitive to tigecycline [minimum inhibitory concentration (MIC) of 0.125 mg/L]. Following tigecycline therapy, the second isolate in each pair demonstrated increased resistance to tigecycline. Two isolates (1R and 2R) were resistant (MIC of 8 mg/L) and one isolate (3I) demonstrated reduced susceptibility (MIC of 0.5 mg/L). Mutations distinguishing each pair of sensitive and resistant isolates were determined through alignment to a reference genome and variant detection. In addition, a de novo assembly of each isolate genome was constructed to confirm mutations. A total of 16 mutations in eleven coding sequences were determined. Mutations in the rpsJ gene, which encodes a structural protein forming part of the 30S ribosomal subunit, were detected in each of the pairs. Mutations were in regions proximal to the predicted tigecycline-binding site. Predicted amino acid substitutions were detected in 1R and 3I. The resistant strains were additionally associated with deletions of 15 nucleotides (2R) and 3 nucleotides (1R). This study confirms that amino acid substitutions in rpsJ contribute towards reduced susceptibility to tigecycline and suggests that deletions may be required for tigecycline resistance in E. faecium.",
keywords = "Enterococcus, Tigecycline, Resistance, Whole-genome sequencing",
author = "Marc Niebel and Joshua Quick and Prieto, {Ana Maria Guzman} and Hill, {Robert L R} and Rachel Pike and Damon Huber and Miruna David and Michael Hornsey and David Wareham and Beryl Oppenheim and Neil Woodford and {van Schaik}, Willem and Nicholas Loman",
note = "Copyright {\textcopyright} 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.",
year = "2015",
month = aug,
day = "20",
doi = "10.1016/j.ijantimicag.2015.07.009",
language = "English",
journal = "International Journal of Antimicrobial Agents",
issn = "0924-8579",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Deletions in a ribosomal protein-coding gene are associated with tigecycline resistance in Enterococcus faecium

AU - Niebel, Marc

AU - Quick, Joshua

AU - Prieto, Ana Maria Guzman

AU - Hill, Robert L R

AU - Pike, Rachel

AU - Huber, Damon

AU - David, Miruna

AU - Hornsey, Michael

AU - Wareham, David

AU - Oppenheim, Beryl

AU - Woodford, Neil

AU - van Schaik, Willem

AU - Loman, Nicholas

N1 - Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

PY - 2015/8/20

Y1 - 2015/8/20

N2 - Enterococcus faecium is an emerging nosocomial pathogen associated with antibiotic therapy in the hospital environment. Whole-genome sequences were determined for three pairs of related, consecutively collected E. faecium clinical isolates to determine putative mechanisms of resistance to tigecycline. The first isolates (1S, 2S and 3S) in each of the three pairs were sensitive to tigecycline [minimum inhibitory concentration (MIC) of 0.125 mg/L]. Following tigecycline therapy, the second isolate in each pair demonstrated increased resistance to tigecycline. Two isolates (1R and 2R) were resistant (MIC of 8 mg/L) and one isolate (3I) demonstrated reduced susceptibility (MIC of 0.5 mg/L). Mutations distinguishing each pair of sensitive and resistant isolates were determined through alignment to a reference genome and variant detection. In addition, a de novo assembly of each isolate genome was constructed to confirm mutations. A total of 16 mutations in eleven coding sequences were determined. Mutations in the rpsJ gene, which encodes a structural protein forming part of the 30S ribosomal subunit, were detected in each of the pairs. Mutations were in regions proximal to the predicted tigecycline-binding site. Predicted amino acid substitutions were detected in 1R and 3I. The resistant strains were additionally associated with deletions of 15 nucleotides (2R) and 3 nucleotides (1R). This study confirms that amino acid substitutions in rpsJ contribute towards reduced susceptibility to tigecycline and suggests that deletions may be required for tigecycline resistance in E. faecium.

AB - Enterococcus faecium is an emerging nosocomial pathogen associated with antibiotic therapy in the hospital environment. Whole-genome sequences were determined for three pairs of related, consecutively collected E. faecium clinical isolates to determine putative mechanisms of resistance to tigecycline. The first isolates (1S, 2S and 3S) in each of the three pairs were sensitive to tigecycline [minimum inhibitory concentration (MIC) of 0.125 mg/L]. Following tigecycline therapy, the second isolate in each pair demonstrated increased resistance to tigecycline. Two isolates (1R and 2R) were resistant (MIC of 8 mg/L) and one isolate (3I) demonstrated reduced susceptibility (MIC of 0.5 mg/L). Mutations distinguishing each pair of sensitive and resistant isolates were determined through alignment to a reference genome and variant detection. In addition, a de novo assembly of each isolate genome was constructed to confirm mutations. A total of 16 mutations in eleven coding sequences were determined. Mutations in the rpsJ gene, which encodes a structural protein forming part of the 30S ribosomal subunit, were detected in each of the pairs. Mutations were in regions proximal to the predicted tigecycline-binding site. Predicted amino acid substitutions were detected in 1R and 3I. The resistant strains were additionally associated with deletions of 15 nucleotides (2R) and 3 nucleotides (1R). This study confirms that amino acid substitutions in rpsJ contribute towards reduced susceptibility to tigecycline and suggests that deletions may be required for tigecycline resistance in E. faecium.

KW - Enterococcus

KW - Tigecycline

KW - Resistance

KW - Whole-genome sequencing

U2 - 10.1016/j.ijantimicag.2015.07.009

DO - 10.1016/j.ijantimicag.2015.07.009

M3 - Article

C2 - 26364847

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

SN - 0924-8579

ER -