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Letter to the Editor

Spread of Klebsiella pneumoniae ST45 Producing GES-5 Carbapenemase or GES-1 Extended-Spectrum β-Lactamase in Newborns and Infants

E. Literacka, R. Izdebski, P. Urbanowicz, D. Żabicka, J. Klepacka, I. Sowa-Sierant, I. Żak, A. Garus-Jakubowska, W. Hryniewicz, M. Gniadkowski
E. Literacka
aDepartment of Epidemiology and Clinical Microbiology, National Reference Centre for Susceptibility Testing, National Medicines Institute, Warsaw, Poland
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R. Izdebski
bDepartment or Molecular Microbiology, National Medicines Institute, Warsaw, Poland
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P. Urbanowicz
bDepartment or Molecular Microbiology, National Medicines Institute, Warsaw, Poland
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D. Żabicka
aDepartment of Epidemiology and Clinical Microbiology, National Reference Centre for Susceptibility Testing, National Medicines Institute, Warsaw, Poland
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J. Klepacka
cDepartment of Clinical Microbiology, University Children’s Hospital, Krakow, Poland
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I. Sowa-Sierant
cDepartment of Clinical Microbiology, University Children’s Hospital, Krakow, Poland
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I. Żak
cDepartment of Clinical Microbiology, University Children’s Hospital, Krakow, Poland
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A. Garus-Jakubowska
dDepartment of Laboratory Diagnostics, Specialist Hospital No. 2, Bytom, Poland
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W. Hryniewicz
aDepartment of Epidemiology and Clinical Microbiology, National Reference Centre for Susceptibility Testing, National Medicines Institute, Warsaw, Poland
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M. Gniadkowski
bDepartment or Molecular Microbiology, National Medicines Institute, Warsaw, Poland
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DOI: 10.1128/AAC.00595-20
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LETTER

GES-type extended-spectrum β-lactamases (ESBLs), such as GES-1, mutate by Gly170Asn/Ser substitutions into carbapenem-hydrolyzing variants, of which GES-5 is seen relatively more frequently (1, 2). In some countries GES-5-producing Enterobacterales have occurred repeatedly in clinical cases and/or outbreaks (1, 3–7) and in hospital or aquatic environmental samples (7–10). blaGES-Like genes reside mainly in class 1 integrons found on diverse plasmids or chromosomes in various species and clones (3, 4, 6–8, 10–12). We report a cluster of infant cases with carbapenem-nonsusceptible GES-positive Klebsiella pneumoniae isolates.

(The results were presented in part at the 28th European Congress of Clinical Microbiology and Infectious Diseases, 21 to 24 April 2018, Madrid, Spain [13].)

Between June 2017 and May 2019, a children’s hospital in Krakow, Poland, recorded 11 unique K. pneumoniae clinical/surveillance isolates, flagged as carbapenemase producers by BD Phoenix (BD, Franklin Lakes, NJ) (Table 1). PCR sequencing identified GES-5 in the first 3 isolates and the GES-1 ESBL in 8 others. In March 2019, a GES-5-producing K. pneumoniae isolate colonized a newborn in Bytom, a city ∼100 km from Krakow. Susceptibility testing by EUCAST guidelines (http://www.eucast.org/) showed resistance of GES-5-positive isolates to all carbapenems, whereas GES-1 isolates had varied carbapenem MICs (see Table S1 in the supplemental material). Failure of a mating-out assay but positive electroporation results indicated that GES-5 and GES-1 were encoded by non–self-transmissible plasmids.

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TABLE 1

Basic clinical epidemiological data for GES-5- and GES-1-producing K. pneumoniae infection/colonization cases

All 12 isolates were sequenced by MiSeq (Illumina, San Diego, CA); contigs were assembled with SPAdes 3.13.2 (14). The first isolate, 4661/17, was also sequenced by MinION (Oxford Nanopore Technologies, Oxford, UK), with hybrid reads assembly by MaSuRCA v.3.2.6 (https://github.com/alekseyzimin/masurca). MLST and core genome MLST (cgMLST), done with BIGSdb (15), revealed that all isolates were ST45 and had 689 identical cgMLST loci. The SNP analysis, utilizing BioNumerics v.7.6.3 (Applied Maths, Sint-Martens-Latem, Belgium) and 4661/17 as a reference, confirmed high genetic homogeneity of the isolates, with 0 to 7 SNPs between the closest relatives (see Fig. S1 in the supplemental material). All K. pneumoniae genomes available at GenBank (n = 8,130 as of 3 December 2019) were screened for ST45 using MLST (https://github.com/tseemann/mlst), which yielded 150 entries. These were aligned against the 4661/17 isolate, inferring SNP-based phylogeny with Parsnp v.1.2 (16). Isolate 4661/17 formed a clade with 31 GES-negative ST45 isolates, recorded mainly and widely in Europe (Fig. 1). The K-type antigen of all Polish isolates was KL24 (https://github.com/katholt/Kaptive).

FIG 1
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FIG 1

SNP-based phylogenetic tree of the GES-5-producing isolate 4661/17 (NMI4661_17) and 31 related K. pneumoniae ST45 isolates, constructed using Parsnp software and visualized with the iTOL tool (https://itol.embl.de). The numbers on the right correspond to assembly numbers available in GenBank.

PlasmidFinder 2.0 (https://cge.cbs.dtu.dk/services/PlasmidFinder/) identified four plasmid replicons in all of the study isolates, i.e., IncFIBK, IncP-6, Col(RNAI), and IncQ2, assigned to circular MinION contigs for 4661/17 (see Table S2 in the supplemental material). blaGES-5/-1 Genes within new class 1 In1525 integrons (dfrB1-blaGES-5/-1-blaOXA-10-aacA4) resided on IncP-6 pKRA-GES-5 plasmids (25,010 bp). Compared with the IncP-6 archetype Rms149 (17), pKRA-GES-5 had an ∼100% identical ∼12.7-kb backbone with partitioning, replication, and mobilization loci (see Fig. S2 in the supplemental material). Similar segments were found in a few more recent plasmids, such as pJF-786 with blaGES-5, but in another integron (GenBank accession no. KX912255). ResFinder 3.2 showed more acquired resistance genes, located on other plasmids (Table S2) (18), and resistomes fit well to resistance patterns. However, carbapenem nonsusceptibility of GES-1 isolates was unclear, despite its regular emergence in ESBL producers by porin deficiency (19). Genes of OmpK36 and OmpK35 porins in the isolates were neither disrupted nor had premature stop codons, but their functionality has not been assessed.

This is one of few reports on carbapenem-resistant Enterobacterales isolates in children in Poland, which surprisingly were GES-5/-1 producers and have still not been recorded in adults. All isolates were of the same genotype, a European-spread K. pneumoniae ST45 sublineage, but with unique blaGES-5/-1 genetic platforms. The temporal replacement of GES-5 isolates by GES-1-positive isolates in Krakow is confusing, considering that reverse GES mutation is unlikely. It might be assumed that a carbapenem-susceptible K. pneumoniae ST45 GES-1 variant has spread in regional pediatric centers, repeatedly segregating resistant variants by GES-1 to GES-5 convergent evolution or unknown auxiliary mechanisms. The epidemiology of GES producers is not completely known, and their prevalence or transmission seems to be underestimated. Broader implementation of genomics in high-quality surveillance may unveil complex and still hidden phenomena (7).

Accession number(s).The nucleotide sequences of the pKRA-GES-5 plasmid, K. pneumoniae 4661_17 chromosome, and pKRA_Col_RNAI, pKRA_IncFIB, and pKRA_IncQ2-like plasmids have been submitted to the GenBank nucleotide sequence database and assigned accession numbers MN436715 and CP050455 to CP050458, respectively.

ACKNOWLEDGMENTS

We thank Anna Baraniak for helpful discussion, Małgorzata Herda and Katarzyna Malinowska for excellent assistance, and Thomas Jové for consultation on the integron analysis.

The study was supported by grants SPUB MIKROBANK from the Polish Ministry of Science and Higher Education, Narodowy Program Ochrony Antybiotyków from the Polish Ministry of Health, and DS-4.47/2018-19 from the National Medicines Institute.

FOOTNOTES

    • Accepted manuscript posted online 6 July 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Nordmann P,
    2. Poirel L
    . 2014. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect 20:821–830. doi:10.1111/1469-0691.12719.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Stewart NK,
    2. Smith CA,
    3. Frase H,
    4. Black DJ,
    5. Vakulenko SB
    . 2015. Kinetic and structural requirements for carbapenemase activity in GES-type β-lactamases. Biochemistry 54:588–597. doi:10.1021/bi501052t.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Aires-de-Sousa M,
    2. Ortiz de la Rosa JM,
    3. Gonçalves ML,
    4. Pereira AL,
    5. Nordmann P,
    6. Poirel L
    . 2019. Epidemiology of carbapenemase-producing Klebsiella pneumoniae in a hospital, Portugal. Emerg Infect Dis 25:1632–1638. doi:10.3201/eid2509.190656.
    OpenUrlCrossRef
  4. 4.↵
    1. Picao RC,
    2. Santos AF,
    3. Nicoletti AG,
    4. Furtado GH,
    5. Gales AC
    . 2010. Detection of GES-5-producing Klebsiella pneumoniae in Brazil. J Antimicrob Chemother 65:796–797. doi:10.1093/jac/dkq024.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Yoon EJ,
    2. Yang JW,
    3. Kim JO,
    4. Lee H,
    5. Lee KJ,
    6. Jeong SH
    . 2018. Carbapenemase-producing Enterobacteriaceae in South Korea: a report from the National Laboratory Surveillance System. Future Microbiol 13:771–783. doi:10.2217/fmb-2018-0022.
    OpenUrlCrossRef
  6. 6.↵
    1. Pedersen T,
    2. Sekyere JO,
    3. Govinden U,
    4. Moodley K,
    5. Sivertsen A,
    6. Samuelsen O,
    7. Essack SY,
    8. Sundsfjord A
    . 2018. Spread of plasmid-encoded NDM-1 and GES-5 carbapenemases among extensively drug-resistant and pandrug-resistant Clinical Enterobacteriaceae in Durban, South Africa. Antimicrob Agents Chemother 62:e02178-17. doi:10.1128/AAC.02178-17.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Ellington MJ,
    2. Davies F,
    3. Jauneikaite E,
    4. Hopkins KL,
    5. Turton JF,
    6. Adams G,
    7. Pavlu J,
    8. Innes AJ,
    9. Eades C,
    10. Brannigan ET,
    11. Findlay J,
    12. White L,
    13. Bolt F,
    14. Kadhani T,
    15. Chow Y,
    16. Patel B,
    17. Mookerjee S,
    18. Otter JA,
    19. Sriskandan S,
    20. Woodford N,
    21. Holmes A
    . 2019. A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid. Clin Infect Dis:ciz1130. doi:10.1093/cid/ciz1130.
    OpenUrlCrossRef
  8. 8.↵
    1. Kim J,
    2. Hong SG,
    3. Bae IK,
    4. Kang JR,
    5. Jeong SH,
    6. Lee W,
    7. Lee K
    . 2011. Emergence of Escherichia coli sequence type ST131 carrying both the blaGES-5 and blaCTX-M-15 genes. Antimicrob Agents Chemother 55:2974–2975. doi:10.1128/AAC.01703-10.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Runcharoen C,
    2. Raven KE,
    3. Reuter S,
    4. Kallonen T,
    5. Paksanont S,
    6. Thammachote J,
    7. Anun S,
    8. Blane B,
    9. Parkhill J,
    10. Peacock SJ,
    11. Chantratita N
    . 2017. Whole genome sequencing of ESBL-producing Escherichia coli isolated from patients, farm waste and canals in Thailand. Genome Med 9:81. doi:10.1186/s13073-017-0471-8.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Girlich D,
    2. Poirel L,
    3. Szczepanowski R,
    4. Schluter A,
    5. Nordmann P
    . 2012. Carbapenem-hydrolyzing GES-5-encoding gene on different plasmid types recovered from a bacterial community in a sewage treatment plant. Appl Environ Microbiol 78:1292–1295. doi:10.1128/AEM.06841-11.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Chen DQ,
    2. Wu AW,
    3. Yang L,
    4. Su DH,
    5. Lin YP,
    6. Hu YW,
    7. Zheng L,
    8. Wang Q
    . 2016. Emergence and plasmid analysis of Klebsiella pneumoniae KP01 carrying blaGES-5 from Guangzhou, China. Antimicrob Agents Chemother 60:6362–6364. doi:10.1128/AAC.00764-16.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Chudejova K,
    2. Rotova V,
    3. Skalova A,
    4. Medvecky M,
    5. Adamkova V,
    6. Papagiannitsis CC,
    7. Hrabak J
    . 2018. Emergence of sequence type 252 Enterobacter cloacae producing GES-5 carbapenemase in a Czech hospital. Diagn Microbiol Infect Dis 90:148–150. doi:10.1016/j.diagmicrobio.2017.10.011.
    OpenUrlCrossRef
  13. 13.↵
    1. Literacka E,
    2. Izdebski R,
    3. Urbanowicz P,
    4. Żabicka D,
    5. Klepacka J,
    6. Sowa-Sierant I,
    7. Żak I,
    8. Garus-Jakubowska A,
    9. Hryniewicz W,
    10. Gniadkowski M
    . 2018. In 28th Eur Congr Clin Microbiol Infect Dis, 21 to 24 April 2018, Madrid, Spain, abstr O0961.
  14. 14.↵
    1. Bankevich A,
    2. Nurk S,
    3. Antipov D,
    4. Gurevich AA,
    5. Dvorkin M,
    6. Kulikov AS,
    7. Lesin VM,
    8. Nikolenko SI,
    9. Pham S,
    10. Prjibelski AD,
    11. Pyshkin AV,
    12. Sirotkin AV,
    13. Vyahhi N,
    14. Tesler G,
    15. Alekseyev MA,
    16. Pevzner PA
    . 2012. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19:455–477. doi:10.1089/cmb.2012.0021.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Bialek-Davenet S,
    2. Criscuolo A,
    3. Ailloud F,
    4. Passet V,
    5. Jones L,
    6. Delannoy-Vieillard A-S,
    7. Garin B,
    8. Le Hello S,
    9. Arlet G,
    10. Nicolas-Chanoine M-H,
    11. Decré D,
    12. Brisse S
    . 2014. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis 20:1812–1820. doi:10.3201/eid2011.140206.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Treangen TJ,
    2. Ondov BD,
    3. Koren S,
    4. Phillippy AM
    . 2014. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 15:524. doi:10.1186/s13059-014-0524-x.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Haines AS,
    2. Jones K,
    3. Cheung M,
    4. Thomas CM
    . 2005. The IncP-6 plasmid Rms149 consists of a small mobilizable backbone with multiple large insertions. J Bacteriol 187:4728–4738. doi:10.1128/JB.187.14.4728-4738.2005.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Zankari E,
    2. Hasman H,
    3. Cosentino S,
    4. Vestergaard M,
    5. Rasmussen S,
    6. Lund O,
    7. Aarestrup FM,
    8. Larsen MV
    . 2012. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 67:2640–2644. doi:10.1093/jac/dks261.
    OpenUrlCrossRefPubMedWeb of Science
  19. 19.↵
    1. Martinez-Martinez L
    . 2008. Extended-spectrum β-lactamases and the permeability barrier. Clin Microbiol Infect 14(Suppl 1):82–89. doi:10.1111/j.1469-0691.2007.01860.x.
    OpenUrlCrossRefPubMedWeb of Science
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Spread of Klebsiella pneumoniae ST45 Producing GES-5 Carbapenemase or GES-1 Extended-Spectrum β-Lactamase in Newborns and Infants
E. Literacka, R. Izdebski, P. Urbanowicz, D. Żabicka, J. Klepacka, I. Sowa-Sierant, I. Żak, A. Garus-Jakubowska, W. Hryniewicz, M. Gniadkowski
Antimicrobial Agents and Chemotherapy Aug 2020, 64 (9) e00595-20; DOI: 10.1128/AAC.00595-20

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Spread of Klebsiella pneumoniae ST45 Producing GES-5 Carbapenemase or GES-1 Extended-Spectrum β-Lactamase in Newborns and Infants
E. Literacka, R. Izdebski, P. Urbanowicz, D. Żabicka, J. Klepacka, I. Sowa-Sierant, I. Żak, A. Garus-Jakubowska, W. Hryniewicz, M. Gniadkowski
Antimicrobial Agents and Chemotherapy Aug 2020, 64 (9) e00595-20; DOI: 10.1128/AAC.00595-20
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KEYWORDS

Enterobacterales
Klebsiella pneumoniae
carbapenemase
extended-spectrum β-lactamase
GES
GES-5

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