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Mechanisms of Resistance

KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity

Laurent Poirel, Xavier Vuillemin, Mario Juhas, Amandine Masseron, Ursina Bechtel-Grosch, Simon Tiziani, Stefano Mancini, Patrice Nordmann
Laurent Poirel
aEmerging Antibiotic Resistance Unit and Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
bSwiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland
cINSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland
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Xavier Vuillemin
aEmerging Antibiotic Resistance Unit and Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
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Mario Juhas
aEmerging Antibiotic Resistance Unit and Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
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Amandine Masseron
aEmerging Antibiotic Resistance Unit and Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
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Ursina Bechtel-Grosch
dDepartment of Trauma Surgery, University Hospital of Zürich, Zürich, Switzerland
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Simon Tiziani
eInstitute of Intensive Medicine, University Hospital Zürich, University of Zürich, Zürich, Switzerland
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Stefano Mancini
fInstitute of Medical Microbiology, University of Zürich, Zürich, Switzerland
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Patrice Nordmann
aEmerging Antibiotic Resistance Unit and Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
bSwiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland
cINSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland
gInstitut for Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland
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DOI: 10.1128/AAC.00321-20
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ABSTRACT

KPC-50 is a KPC-3 variant identified from a Klebsiella pneumoniae clinical isolate recovered in Switzerland in 2019. Compared to KPC-3, KPC-50 shows (i) a three-amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277, (ii) an increased affinity to ceftazidime, (iii) a decreased sensitivity to avibactam, explaining the ceftazidime-avibactam resistance, and (iv) an association with a sharp reduction of its carbapenemase activity.

INTRODUCTION

The occurrence of multidrug-resistant Enterobacterales, especially carbapenemase-producing isolates, is increasingly reported, leaving very few therapeutic options for treating related infections (1). Interestingly, the recently marketed ceftazidime-avibactam (CZA) drug combination offers novel perspectives (2). This β-lactam/β-lactamase inhibitor combination provides a therapeutic alternative for treating infections caused by KPC-like and OXA-48-like producers, whereas producers of carbapenemases of the metallo-β-lactamase type remain resistant to that combination (1, 2). Despite CZA being rarely prescribed worldwide, KPC-like-producing isolates resistant to this drug combination have already been reported (3–7). Several reports identified KPC variants exhibiting single-amino-acid substitutions in their omega-loop (amino acid positions 164 to 179), particularly the Asp179Tyr substitution, leading to enhanced affinity toward ceftazidime with a concomitant reduced binding to avibactam (AVI) (8–12). In addition, we recently identified KPC-41, possessing a three-amino-acid insertion in the KPC-3 protein sequence and being distantly located from the omega loop (namely, between positions 269 and 270), that conferred high levels of resistance to CZA in a clinical Klebsiella pneumoniae isolate recovered in Switzerland (13).

K. pneumoniae isolate N869 was recovered from a patient repatriated from Greece to Switzerland after a traffic accident. In the Greek hospital, the patient developed ventilator-associated pneumonia, for which he received a treatment made of clindamycin, linezolid, and meropenem for 2 days, to which colistin was added on day 5. A few days later, he was transferred to Switzerland, where all antibiotics but meropenem (as monotherapy) were discontinued. Rectal swabs performed at admission grew K. pneumoniae isolate N859 using the Chrom ID Carba Smart selective plate (bioMérieux, La Balme-les-Grottes, France). According to the EUCAST 2020 breakpoints (14), K. pneumoniae isolate N859 was resistant to all β-lactams, including imipenem and ertapenem, but remained susceptible to meropenem (Table 1). The carbapenemase activity was evaluated by using the Rapid Carba NP test, which gave a positive result (15).

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TABLE 1

MICs of β-lactams for K. pneumoniae clinical isolate N859, E. coli TOP10 recombinant strains producing KPC-50 and KPC-3, and E. coli TOP10 recipient strain

K. pneumoniae N859 was also resistant to aminoglycosides (kanamycin, tobramycin, and netilmicin), to fluoroquinolones, and to colistin (MIC at 128 μg/ml). It remained susceptible to tetracycline, tigecycline, chloramphenicol, trimethoprim-sulfamethoxazole, and fosfomycin and was of intermediate susceptibility to amikacin and gentamicin. It also showed resistance to CZA (MIC of >256 μg/ml) and to a ceftolozane-tazobactam combination (>256 μg/ml), using inhibitor concentrations of 4 μg/ml.

PCR identified a blaKPC-like gene, and sequencing of the corresponding amplicon identified a gene encoding a KPC variant possessing a three-amino-acid insertion (Glu-Ala-Val) between amino acids 276 and 277 (Ambler numbering), leading to a novel variant named KPC-50 (see Fig. S1 in the supplemental material). A search for additional β-lactamase resistance genes, as reported previously (16), identified a blaSHV-like gene (intrinsic to K. pneumoniae) but no additional extended-spectrum β-lactamase gene. Mating-out assays performed using K. pneumoniae N859 as the donor and azide-resistant Escherichia coli J53 strain as the recipient (13) were successful and confirmed the plasmid location of the blaKPC-50 gene, being ca. 60 kb in size (data not shown). No other antibiotic marker was cotransferred along with the blaKPC-50 gene. PCR-based replicon typing showed that this plasmid belonged to the IncFIB incompatibility group (17). Multilocus sequence typing, performed as described previously (18), showed that isolate N859 belonged to sequence type ST258, which corresponds to the worldwide spread of the KPC-producing K. pneumoniae background (19, 20).

To confirm whether the amino acid substitutions identified within the KPC sequence was responsible for the CZA resistance phenotype observed in K. pneumoniae N859, the blaKPC-50 gene was cloned and expressed in E. coli TOP10. MIC values then were compared with those of the previously obtained KPC-3-producing E. coli TOP10 (13). In such an E. coli background, KPC-3 conferred resistance to all β-lactams, including ceftazidime, but remained susceptible to CZA, as previously shown (13). Conversely, although KPC-50 also conferred high-level resistance to ceftazidime, it additionally conferred high-level resistance to CZA (Table 1). It is worth noting that KPC-50 conferred much lower levels of resistance to cefoxitin, cefotaxime, and cefepime than KPC-3. One of the most marked features of KPC-50 compared to KPC-3 was that its production did not lead to resistance to carbapenems (Table 1). Indeed, E. coli expressing the blaKPC-50 gene remained susceptible to ertapenem and meropenem (MICs of 0.25 μg/ml and 0.5 μg/ml, respectively), while the MIC of imipenem observed for the KPC-50-producing E. coli recombinant strain was 4 μg/ml (breakpoint value). Low MICs were observed when testing the new carbapenem–β-lactamase inhibitor combinations, such as imipenem-relebactam, and, more specifically, meropenem-vaborbactam showed an excellent capacity to inhibit the growth of KPC-50 producers (Table 1).

The enzymatic properties of KPC-50 were determined using purified extracts and compared to those of KPC-3 previously obtained under the same conditions (13). Kinetic data showed that KPC-50 has a lower hydrolysis activity of cefalotin, cefotaxime, aztreonam, and imipenem than those of KPC-3 (Table 2). Similar decreased hydrolytic properties toward β-lactams have been reported previously for those KPC variants conferring resistance to the CZA combination, such as KPC-41 (13) or the Asp179Tyr KPC-2 mutants (21–23). Furthermore, the activity of KPC-50 toward aztreonam was not detectable, in contrast to KPC-3 (Table 2) and also contrasting with data obtained for KPC-41 (13).

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TABLE 2

Kinetic parameters of purified β-lactamases KPC-50 and KPC-3a

Kinetic activities toward ceftazidime were measured and compared for KPC-50 and KPC-3 enzymes. As expected, a significant hydrolysis rate was detected with KPC-3, but no hydrolysis could be detected with KPC-50 under normal conditions (measurement made during 5 min). Another assay was performed for 1 h, showing that ceftazidime was indeed hydrolyzed by KPC-50, but the hydrolysis rate was much lower than that of KPC-3 (Fig. 1). Therefore, we observed a paradoxical situation here, with KPC-50 conferring high-level resistance to ceftazidime once produced by a recombinant E. coli clone but a weak hydrolysis rate as measured by UV spectrophotometry. Thus, affinities of KPC-50 and KPC-3 compared to those of the ceftazidime substrate were measured using various concentrations of ceftazidime to inhibit the hydrolysis of a reporter substrate (nitrocefin), as published previously (10, 13). At the same ceftazidime concentrations, a higher inhibition level of nitrocefin was observed with KPC-50 than with KPC-3 (Fig. 1), showing that KPC-50 exhibited a higher affinity toward ceftazidime than KPC-3.

FIG 1
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FIG 1

Analysis of ceftazidime hydrolysis. (A) KPC-50 and KPC-3 (1 μM enzyme) hydrolysis of 25 μM ceftazidime (CAZ) at room temperature. (B and C) Competitive inhibition curves determined with 50 μM nitrocefin and increasing concentrations of CAZ with 0.1 μM KPC-50 (B) and 0.1 μM KPC-3 (C) at room temperature. Nitrocefin absorbance was measured.

Comparative inhibitory activities of clavulanic acid, tazobactam, and AVI were determined for KPC-50 and KPC-3, showing a 4-fold lower inhibitory activity of AVI toward KPC-50 than KPC-3; conversely, those of tazobactam and clavulanic acid were higher toward KPC-50 than KPC-3 (Table 2).

Overall, these results indicated that the 276-Glu-Ala-Val-277 insertion observed in the KPC-50 sequence was responsible for the reduced hydrolysis of cefalotin, cefotaxime, and carbapenems, associated with a higher affinity toward ceftazidime and a reduced sensitivity to AVI.

Conclusions.A novel KPC-type enzyme conferring resistance to CZA was identified here from a multidrug-resistant K. pneumoniae isolate recovered in Switzerland but likely acquired in Greece, with no known history of treatment with CZA for the patient. Of note, and as already highlighted for KPC-41 and other KPC mutants conferring resistance to CZA, the overall decreased carbapenemase activity observed for KPC-50 might be considered good news. Furthermore, the newly developed carbapenem–β-lactamase inhibitor combinations (meropenem-vaborbactam and imipenem-relebactam) also showed an excellent efficacy against the KPC-50 producers (either the K. pneumoniae clinical isolate or the E. coli recombinant strain).

Data availability.The sequence of KPC-50 has been deposited in the NCBI database under GenBank accession number MN654342.

ACKNOWLEDGMENTS

This work was financed by the University of Fribourg, Switzerland, the NARA, and the Swiss National Science Foundation (projects FNS-31003A_163432 and FNS-407240_177381).

L.P. and P.N. designed the study. S.M. provided the material. U.B.-G. and S.T. provided the clinical data. X.V., M.J., and A.M. performed the experiments. L.P. and P.N. wrote the manuscript.

FOOTNOTES

    • Received 18 February 2020.
    • Returned for modification 26 March 2020.
    • Accepted 13 May 2020.
    • Accepted manuscript posted online 26 May 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
    . 2019. Epidemiology and diagnostics of carbapenem resistance in Gram-negative bacteria. Clin Infect Dis 69:S521–S528. doi:10.1093/cid/ciz824.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Van Duin D,
    2. Bonomo RA
    . 2016. Ceftazidime/avibactam and ceftolozane/tazobactam: second-generation β-lactam/β-lactamase inhibitor combinations. Clin Infect Dis 63:234–241. doi:10.1093/cid/ciw243.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Humphries RM,
    2. Yang S,
    3. Hemarajata P,
    4. Ward KW,
    5. Hindler JA,
    6. Miller SA,
    7. Gregson A
    . 2015. First report of ceftazidime-avibactam resistance in a KPC-3-expressing Klebsiella pneumoniae isolate. Antimicrob Agents Chemother 59:6605–6607. doi:10.1128/AAC.01165-15.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Shields RK,
    2. Chen L,
    3. Cheng S,
    4. Chavda KD,
    5. Press EG,
    6. Snyder A,
    7. Pandey R,
    8. Doi Y,
    9. Kreiswirth BN,
    10. Nguyen MH,
    11. Clancy CJ
    . 2017. Emergence of ceftazidime-avibactam mutations during treatment. Antimicrob Agents Chemother 61:e02097-16. doi:10.1128/AAC.02097-16.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Hemarajata P,
    2. Humphries RM
    . 2019. Ceftazidime/avibactam resistance associated with L169P mutation in the omega loop of KPC-2. J Antimicrob Chemother 74:1241–1243. doi:10.1093/jac/dkz026.
    OpenUrlCrossRef
  6. 6.↵
    1. Räisänen K,
    2. Koivula I,
    3. Ilmavirta H,
    4. Puranen S,
    5. Kallonen T,
    6. Lyytikäinen O,
    7. Jalava J
    . 2019. Emergence of ceftazidime-avibactam-resistant Klebsiella pneumoniae during treatment, Finland, December 2018. Euro Surveill 24:1900256. doi:10.2807/1560-7917.ES.2019.24.19.1900256.
    OpenUrlCrossRef
  7. 7.↵
    1. Athans V,
    2. Neuner EA,
    3. Hassouna H,
    4. Richter SS,
    5. Keller G,
    6. Castanheira M,
    7. Brizendine KD,
    8. Mathers AJ
    . 2018. Meropenem-vaborbactam as salvage therapy for ceftazidime-avibactam-resistant Klebsiella pneumoniae bacteremia and abscess in a liver transplant recipient. Antimicrob Agents Chemother 63:e01551-18. doi:10.1128/AAC.01551-18.
    OpenUrlCrossRef
  8. 8.↵
    1. Barnes MD,
    2. Winkler ML,
    3. Taracila MA,
    4. Page MG,
    5. Desarbre E,
    6. Kreiswirth BN,
    7. Shields RK,
    8. Nguyen MH,
    9. Clancy C,
    10. Spellberg B,
    11. Papp-Wallace KM,
    12. Bonomo RA
    . 2017. Klebsiella pneumoniae carbapenemase-2 (KPC-2), substitutions at Ambler position Asp179, and resistance to ceftazidime-avibactam: unique antibiotic-resistant phenotypes emerge from β-lactamase protein engineering. mBio 8:e00528-17. doi:10.1128/mBio.00528-17.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Livermore DM,
    2. Warner M,
    3. Jamrozy D,
    4. Mushtaq S,
    5. Nichols WW,
    6. Mustafa N,
    7. Woodford N
    . 2015. In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase. Antimicrob Agents Chemother 59:5324–5330. doi:10.1128/AAC.00678-15.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Winkler ML,
    2. Papp-Wallace KM,
    3. Bonomo RA
    . 2015. Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop. J Antimicrob Chemother 70:2279–2286. doi:10.1093/jac/dkv094.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Compain F,
    2. Arthur M
    . 2017. Impaired inhibition by avibactam and resistance to the ceftazidime-avibactam. Antimicrob Agents Chemother 61:e00451-17. doi:10.1128/AAC.00451-17.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Galani I,
    2. Antoniadou A,
    3. Karaiskos I,
    4. Kontopoulou K,
    5. Giamarellou H,
    6. Souli M
    . 2019. Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam. Clin Microbiol Infect 25:e5–e763. doi:10.1016/j.cmi.2019.03.011.
    OpenUrlCrossRef
  13. 13.↵
    1. Mueller L,
    2. Masseron A,
    3. Prod’Hom G,
    4. Galperine T,
    5. Greub G,
    6. Poirel L,
    7. Nordmann P
    . 2019. Phenotypic, biochemical and genetic analysis of KPC-41, a KPC-3 variant conferring resistance to ceftazidime-avibactam and exhibiting reduced carbapenemase activity. Antimicrob Agents Chemother 63:e01111-19. doi:10.1128/AAC.01111-19.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    EUCAST. 2020. Breakpoints tables for interpretation of MICs and zone diameters. Version 10. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_10_Breakpoint_Tables.pdf.
  15. 15.↵
    1. Nordmann P,
    2. Poirel L,
    3. Dortet L
    . 2012. Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 18:1503–1507. doi:10.3201/eid1809.120355.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Girlich D,
    2. Naas T,
    3. Leelaporn A,
    4. Poirel L,
    5. Fennewald M,
    6. Nordmann P
    . 2002. Nosocomial spread of the integron-located veb-1-like cassette encoding an extended-spectrum ß-lactamase in Pseudomonas aeruginosa in Thailand. Clin Infect Dis 34:175–182. doi:10.1086/338786.
    OpenUrlCrossRef
  17. 17.↵
    1. Carattoli A,
    2. Bertini A,
    3. Villa L,
    4. Falbo V,
    5. Hopkins KL,
    6. Threlfall EJ
    . 2005. Identification of plasmids by PCR-based replicon typing. J Microbiol Methods 63:219–228. doi:10.1016/j.mimet.2005.03.018.
    OpenUrlCrossRefPubMedWeb of Science
  18. 18.↵
    1. Diancourt L,
    2. Passet V,
    3. Verhoef J,
    4. Grimont PA,
    5. Brisse S
    . 2005. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol 43:4178–4182. doi:10.1128/JCM.43.8.4178-4182.2005.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Pitout JD,
    2. Nordmann P,
    3. Poirel L
    . 2015. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother 59:5873–5884. doi:10.1128/AAC.01019-15.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Munoz-Price LS,
    2. Poirel L,
    3. Bonomo RA,
    4. Schwaber MJ,
    5. Daikos GL,
    6. Cormican M,
    7. Cornaglia G,
    8. Garau J,
    9. Gniadkowski M,
    10. Hayden MK,
    11. Kumarasamy K,
    12. Livermore DM,
    13. Maya JJ,
    14. Nordmann P,
    15. Patel JB,
    16. Paterson DL,
    17. Pitout J,
    18. Villegas MV,
    19. Wang H,
    20. Woodford N,
    21. Quinn JP
    . 2013. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 13:785–796. doi:10.1016/S1473-3099(13)70190-7.
    OpenUrlCrossRefPubMedWeb of Science
  21. 21.↵
    1. Haidar G,
    2. Clancy CJ,
    3. Shields RK,
    4. Hao B,
    5. Cheng S,
    6. Nguyen MH
    . 2017. Mutations in blaKPC-3 that confer ceftazidime-avibactam resistance encode novel KPC-3 variants that function as extended-spectrum β-lactamases. Antimicrob Agents Chemother 61:e02534-16. doi:10.1128/AAC.02534-16.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Shields RK,
    2. Nguyen MH,
    3. Press EG,
    4. Chen L,
    5. Kreiswirth BN,
    6. Clancy CJ
    . 2017. Emergence of ceftazidime-avibactam resistance and restoration of carbapenem susceptibility in Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: a case report and review of literature. Open Forum Infect Dis 4:ofx101. doi:10.1093/ofid/ofx101.
    OpenUrlCrossRef
  23. 23.↵
    1. Shields RK,
    2. Nguyen MH,
    3. Press EG,
    4. Chen L,
    5. Kreiswirth BN,
    6. Clancy CJ
    . 2017. In vitro selection of meropenem resistance among ceftazidime-avibactam-resistant, meropenem-susceptible Klebsiella pneumoniae isolates with variant KPC-3 carbapenemases. Antimicrob Agents Chemother 61:e00079-17. doi:10.1128/AAC.00079-17.
    OpenUrlAbstract/FREE Full Text
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KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity
Laurent Poirel, Xavier Vuillemin, Mario Juhas, Amandine Masseron, Ursina Bechtel-Grosch, Simon Tiziani, Stefano Mancini, Patrice Nordmann
Antimicrobial Agents and Chemotherapy Jul 2020, 64 (8) e00321-20; DOI: 10.1128/AAC.00321-20

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KPC-50 Confers Resistance to Ceftazidime-Avibactam Associated with Reduced Carbapenemase Activity
Laurent Poirel, Xavier Vuillemin, Mario Juhas, Amandine Masseron, Ursina Bechtel-Grosch, Simon Tiziani, Stefano Mancini, Patrice Nordmann
Antimicrobial Agents and Chemotherapy Jul 2020, 64 (8) e00321-20; DOI: 10.1128/AAC.00321-20
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KEYWORDS

KPC
ceftazidime-avibactam
Klebsiella pneumoniae

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