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Whole-genome comparison of two Acinetobacter baumannii isolates from a single patient, where resistance developed during tigecycline therapy

Hornsey, M. and Loman, N. J. and Wareham, D. W. and Ellington, M. J. and Pallen, M. J. and Turton, J. F. and Underwood, A. and Gaulton, T. and Thomas, C. P. and Doumith, M. and Livermore, D. M. and Woodford, N. (2011) Whole-genome comparison of two Acinetobacter baumannii isolates from a single patient, where resistance developed during tigecycline therapy. Journal of Antimicrobial Chemotherapy, 66 (7). pp. 1499-1503. ISSN 0305-7453

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URL of Published Version: http://dx.doi.org/10.1093/jac/dkr168

Identification Number/DOI: 10.1093/jac/dkr168

Objectives: The whole genomes of two Acinetobacter baumannii isolates recovered from a single patient were sequenced to gain insight into the nature and extent of genomic plasticity in this important nosocomial pathogen over the course of a short infection. The first, AB210, was recovered before tigecycline therapy and was susceptible to this agent; the second, AB211, was recovered after therapy and was resistant.
Methods: DNA from AB210 was sequenced by 454 GS FLX pyrosequencing according to the standard protocol for whole-genome shotgun sequencing, producing ~250 bp fragment reads. AB211 was shotgun sequenced using the Illumina Genetic Analyzer to produce fragment reads of exactly 36 bp. Single nucleotide polymorphisms (SNPs) and large deletions detected in AB211 in relation to AB210 were confirmed by PCR and DNA sequencing.
Results: Automated gene prediction detected 3850 putative coding sequences (CDSs). Sequence analysis demonstrated the presence of plasmids pAB0057 and pACICU2 in both isolates. Eighteen putative SNPs were detected between the pre- and post-therapy isolates, AB210 and AB211. Three contigs in AB210 were not covered by reads in AB211, representing three deletions of ~15, 44 and 17 kb.
Conclusions: This study demonstrates that significant differences were detectable between two bacterial isolates recovered 1 week apart from the same patient, and reveals the potential of whole-genome sequencing as a tool for elucidating the processes responsible for changes in antibiotic susceptibility profiles.

Type of Work:Article
Date:May 2011 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Keywords:OXA-23 clone 1; glycylcycline resistance; comparative genomics
Subjects:QH426 Genetics
QR180 Immunology
RA Public aspects of medicine
Institution:University of Birmingham
Copyright Holders:Published by Oxford University Press on behalf of The British Society for Antimicrobial Chemotherapy
ID Code:1164
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