title: Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae.
abstract: 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.
authors.affiliation: The University of Queensland, Centre for Clinical Research (UQCCR), Herston QLD 4029, Australia.|Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.|College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.|World Health Organization Collaborating Centre for Infection Prevention and Control, and the Gulf Cooperation Council Center for Infection Control, Riyadh, Saudi Arabia.
authors.forename: Hosam M
authors.initials: HM
authors.lastname: Zowawi
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.|School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Forde
authors.affiliation: Pathology and Laboratory Medicine Department at Sheikh Khalifa General Hospital, Umm Al Quwain, United Arab Emirates.
authors.forename: Mubarak
authors.initials: M
authors.lastname: Alfaresi
authors.affiliation: Urology Department, Sheikh Khalifa General Hospital, Umm Al Quwain, United Arab Emirates.
authors.forename: Abdulqadir
authors.initials: A
authors.lastname: Alzarouni
authors.affiliation: Urology Department, Sheikh Khalifa General Hospital, Umm Al Quwain, United Arab Emirates.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Farahat
authors.affiliation: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Teik-Min
authors.initials: TM
authors.lastname: Chong
authors.affiliation: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Wai-Fong
authors.initials: WF
authors.lastname: Yin
authors.affiliation: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kok-Gan
authors.initials: KG
authors.lastname: Chan
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.|School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schembri
authors.affiliation: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.|School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.affiliation: The University of Queensland, Centre for Clinical Research (UQCCR), Herston QLD 4029, Australia.|Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
mesh_terms: D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology; D002876:Chromosomes, Bacterial; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D018628:Gene Dosage; D023061:Gene Order; D016680:Genome, Bacterial; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D008826:Microbial Sensitivity Tests; D016254:Mutagenesis, Insertional; D010641:Phenotype
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004251:DNA Transposable Elements