Data_Sheet_1_Genomic Epidemiology of Carbapenem- and Colistin-Resistant Klebsiella pneumoniae Isolates From Serbia: Predominance of ST101 Strains Carrying a Novel OXA-48 Plasmid.xlsx
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 MgrBC28S 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 blaOXA–48 genetic background. The blaOXA–48 gene was located in a novel IncFIA-IncR hybrid plasmid, also containing the extended spectrum β-lactamase-encoding gene blaCTX–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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References
- https://doi.org//10.1186/1471-2164-12-402
- https://doi.org//10.1128/aac.42.7.1636
- https://doi.org//10.1128/AAC.02457-17
- https://doi.org//10.1089/cmb.2012.0021
- https://doi.org//10.1080/14787210.2018.1522249
- https://doi.org//10.1128/AAC.02669-14
- https://doi.org//10.1371/journal.pone.0133727
- https://doi.org//10.1093/jac/dkx532
- https://doi.org//10.1128/AAC.01480-13
- https://doi.org//10.1128/AAC.02555-14
- https://doi.org//10.1128/AAC03110-14
- https://doi.org//10.1128/AAC.02412-14
- https://doi.org//10.1128/mBio.01355-1314
- https://doi.org//10.1186/1423-0127-17-60
- https://doi.org//10.1128/AAC.04763-14
- https://doi.org//10.1186/s12866-015-0510-9
- https://doi.org//10.1038/s41564-019-0492-8
- https://doi.org//10.1016/S1473-3099(16)30257-2
- https://doi.org//10.1128/AAC.00084-14
- https://doi.org//10.1080/17425255.2017.1230200
- https://doi.org//10.1128/AAC.00592-18
- https://doi.org//10.1007/978-1-4939-6958-6_17
- https://doi.org//10.1093/nar/gkw290
- https://doi.org//10.1038/s41598-017-04793-4
- https://doi.org//10.1128/JB.06055-11
- https://doi.org//10.1128/AAC.00580-17
- https://doi.org//10.1128/AAC.00525-16
- https://doi.org//10.1128/AAC.00838-12
- https://doi.org//10.1093/femsre/fux013
- https://doi.org//10.3201/eid2206.151840
- https://doi.org//10.1128/AAC.02550-16
- https://doi.org//10.1016/j.ijantimicag.2014.07.020
- https://doi.org//10.1128/MMBR.00078-15
- https://doi.org//10.1128/AAC.00329-311
- https://doi.org//10.1128/AAC.05289-5211
- https://doi.org//10.2807/1560-7917.es2013.18.31.20549
- https://doi.org//10.3389/fmicb.2019.00542
- https://doi.org//10.1016/j.ijantimicag.2014.05.008
- https://doi.org//10.1128/AAC.01889-16
- https://doi.org//10.1128/AAC.01195-18
- https://doi.org//10.1093/bioinformatics/btr039
- https://doi.org//10.1016/j.tim.2018.02.006
- https://doi.org//10.1111/j.1469-0691.2007.01708.x
- https://doi.org//10.1186/s13059-014-0524-x
- https://doi.org//10.2298/VSP150917260T
- https://doi.org//10.1371/journal.pcbi.1005595
- https://doi.org//10.1128/AAC.01947-13
- https://doi.org//10.1128/AAC.04037-4014
- https://doi.org//10.1093/gbe/evv062
- https://doi.org//10.1099/mgen.0.000102
- https://doi.org//10.1093/jac/dks261