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Emergence of mobile colistin resistance (mcr-8) in a highly successful Klebsiella pneumoniae sequence type 15 clone from clinical infections in Bangladesh

Farzana, Refath, Jones, Lim S., Barratt, Andrew, Rahman, Muhammad Anisur, Sands, Kirsty, Portal, Edward, Boostrom, Ian, Espina, Laura, Pervin, Monira, Uddin, A. K. M. Nasir and Walsh, Timothy R. 2020. Emergence of mobile colistin resistance (mcr-8) in a highly successful Klebsiella pneumoniae sequence type 15 clone from clinical infections in Bangladesh. mSphere 5 (2) , e00023-20. 10.1128/mSphere.00023-20

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The emergence of mobilized colistin resistance genes (mcr) has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. In this study, colistin-resistant Klebsiella pneumoniae harboring mcr-8.1 was recovered from infected patients in the largest public hospital of Bangladesh, with a prevalence of 0.3% (3/1,097). We found mcr-8.1 in an identical highly stable multidrug-resistant IncFIB(pQil) plasmid of ∼113 kb, which belonged to an epidemiologically successful K. pneumoniae clone, ST15. The resistance mechanism was proven to be horizontally transferable, which incurred a fitness cost to the host. The core genome phylogeny suggested the clonal spread of mcr-8.1 in a Bangladeshi hospital. Core genome single-nucleotide polymorphisms among the mcr-8.1-positive K. pneumoniae isolates ranged from 23 to 110. It has been hypothesized that mcr-8.1 was inserted into IncFIB(pQil) with preexisting resistance loci, blaTEM-1b and blaCTX-M-15, by IS903B. Coincidentally, all resistance determinants in the plasmid [mcr-8.1, ampC, sul2, 1d-APH(6), APH(3′′)-Ib, blaTEM-1b, blaCTX-M-15] were bracketed by IS903B, demonstrating the possibility of intra- and interspecies and intra- and intergenus transposition of entire resistance loci. This is the first report of an mcr-like mechanism from human infections in Bangladesh. However, given the acquisition of mcr-8.1 by a sable conjugative plasmid in a successful high-risk clone of K. pneumoniae ST15, there is a serious risk of dissemination of mcr-8.1 in Bangladesh from 2017 onwards.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Society for Microbiology: Open Access Journals / American Society for Microbiology
ISSN: 2379-5042
Date of First Compliant Deposit: 1 April 2020
Date of Acceptance: 27 February 2020
Last Modified: 11 May 2020 13:54

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