Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae

Zowawi, H.M. and Forde, B.M. and Alfaresi, M. and Alzarouni, A. and Farahat, Y. and Chong, T.M. and Yin, Wai Fong and Chan, Kok Gan and Li, J. and Schembri, M.A. and Beatson, S.A. and Paterson, D.L. (2015) Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae. Scientific Reports, 5. p. 15082. ISSN 2045-2322, DOI

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Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. Using Single Molecule Real Time (SMRT) sequencing we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. The precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Intriguingly, we identified three chromosomal copies of an ISEcp1-bla OXA-181 mobile element, one of which has disrupted the mgrB regulatory gene, accounting for resistance to colistin. Our findings provide the first description of pandrug-resistant CRE at the genomic level, and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics.

Item Type: Article
Funders: Australian National Health and Medical Research Council (APP1033799), University of Malaya High Impact Research (HIR) Grants (UM-MOHE HIR Grant UM.C/625/1/HIR/MOHE/CHAN/14/1, Grant No. H-50001-A000027 and H00001-A000001), NHMRC Career Development Fellowship (APP1090456), Australian Research Council Future Fellowship (FT100100662)
Uncontrolled Keywords: Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Chromosomes, Bacterial; DNA Transposable Elements; Drug Resistance, Bacterial; Evolution, Molecular; Gene Dosage; Gene Order; Genome, Bacterial; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Mutagenesis, Insertional; Phenotype
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 18 Sep 2018 09:30
Last Modified: 23 Dec 2019 05:45

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