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Title
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Genomic epidemiology of carbapenem- and colistin-resistant Klebsiella pneumoniae isolates from Serbia : predominance of ST101 strains carrying a novel OXA-48 plasmid
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Author
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Abstract
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| Klebsiella pneumoniae is a major cause of severe healthcare-associated infections and often shows MDR phenotypes. Carbapenem resistance is frequent, and colistin represents a key molecule to treat infections caused by such isolates. Here we evaluated the antimicrobial resistance (AMR) mechanisms and the genomic epidemiology of clinical K. pneumoniae isolates from Serbia. Consecutive non-replicate K. pneumoniae clinical isolates (n = 2,298) were collected from seven hospitals located in five Serbian cities and tested for carbapenem resistance by disk diffusion. Isolates resistant to at least one carbapenem (n = 426) were further tested for colistin resistance with Etest or Vitek2. Broth microdilution (BMD) was performed to confirm the colistin resistance phenotype, and colistin-resistant isolates (N = 45, 10.6%) were characterized by Vitek2 and whole genome sequencing. Three different clonal groups (CGs) were observed: CG101 (ST101, N = 38), CG258 (ST437, N = 4; ST340, N = 1; ST258, N = 1) and CG17 (ST336, N = 1). mcr genes, encoding for acquired colistin resistance, were not observed, while all the genomes presented mutations previously associated with colistin resistance. In particular, all strains had a mutated MgrB, with MgrB(C28S) being the prevalent mutation and associated with ST101. Isolates belonging to ST101 harbored the carbapenemase OXA-48, which is generally encoded by an IncL/M plasmid that was no detected in our isolates. MinION sequencing was performed on a representative ST101 strain, and the obtained long reads were assembled together with the Illumina high quality reads to decipher the bla(OXA-)(48) genetic background. The bla(OXA-)(48) gene was located in a novel IncFIA-IncR hybrid plasmid, also containing the extended spectrum beta-lactamase-encoding gene bla(CTX-M-15) and several other AMR genes. Non-ST101 isolates presented different MgrB alterations (C28S, C28Y, K2*, K3*, Q30*, adenine deletion leading to frameshift and premature termination, IS5-mediated inactivation) and expressed different carbapenemases: OXA-48 (ST437 and ST336), NDM-1 (ST437 and ST340) and KPC-2 (ST258). Our study reports the clonal expansion of the newly emerging ST101 clone in Serbia. This high-risk clone appears adept at acquiring resistance, and efforts should be made to contain the spread of such clone. |
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Language
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English
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Source (journal)
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Frontiers in microbiology. - Lausanne, 2010, currens
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Publication
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Lausanne
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Frontiers Research Foundation
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2020
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ISSN
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1664-302X
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DOI
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10.3389/FMICB.2020.00294
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Volume/pages
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11
(2020)
, p. 1-10
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Article Reference
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294
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ISI
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000523646100001
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Pubmed ID
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32153554
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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