Cited by 1,639Antibiotic Resistance in BacteriaEnterobacteriaceae and Cronobacter ResearchPharmaceutical and Antibiotic Environmental Impacts

Novel Carbapenem-Hydrolyzing β-Lactamase, KPC-1, from a Carbapenem-Resistant Strain of Klebsiella pneumoniae

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Yigit, Hesna, Queenan, Anne Marie, Anderson, Gregory J., Domenech-Sanchez, Antonio, Biddle, James W., Steward, Christine D., Alberti, Sebastian, Bush, Karen +1 more·2001·Antimicrobial Agents and Chemotherapy

Abstract

A Klebsiella pneumoniae isolate showing moderate to high-level imipenem and meropenem resistance was investigated. The MICs of both drugs were 16 μg/ml. The β-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. The strain was also resistant to extended-spectrum cephalosporins and aztreonam. Isoelectric focusing studies demonstrated three β-lactamases, with pIs of 7.2 (SHV-29), 6.7 (KPC-1), and 5.4 (TEM-1). The presence of bla SHV and bla TEM genes was confirmed by specific PCRs and DNA sequence analysis. Transformation and conjugation studies with Escherichia coli showed that the β-lactamase with a pI of 6.7, KPC-1 ( K. pneumoniae carbapenemase-1), was encoded on an approximately 50-kb nonconjugative plasmid. The gene, bla KPC-1 , was cloned in E. coli and shown to confer resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of the novel carbapenem-hydrolyzing β-lactamase, KPC-1, showed 45% identity to the pI 9.7 carbapenem-hydrolyzing β-lactamase, Sme-1, from Serratia marcescens S6. Hydrolysis studies showed that purified KPC-1 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and monobactams. KPC-1 had the highest affinity for meropenem. The kinetic studies also revealed that clavulanic acid and tazobactam inhibited KPC-1. An examination of the outer membrane proteins of the parent K. pneumoniae strain demonstrated that the strain does not express detectable levels of OmpK35 and OmpK37, although OmpK36 is present. We concluded that carbapenem resistance in K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing β-lactamase, KPC-1, although alterations in porin expression may also play a role.

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Crossref · 10.1128/aac.45.4.1151-1161.2001

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  • KPC was first reported in 1996 from a K. pneumoniae recovered from a patient in North Carolina, USA.

    “KPC was first reported in 1996 from a K. pneumoniae recovered from a patient in North Carolina, USA (25).”

    From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [25]

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Authors
Yigit, H., Queenan, A. M., Anderson, G. J., Domenech-Sanchez, A., Biddle, J. W., Steward, C. D., Alberti, S., Bush, K., & Tenover, F. C.
Affiliations
  • Centers for Disease Control and Prevention (US)
  • <!--label omitted: 2-->The R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 088692; and
  • <!--label omitted: 3-->Área de Microbiologia, Universidad de las Islas Baleares, Crtra. Valldemosa, Palma de Mallorca, 07071,3 Spain
  • <!--label omitted: 4-->Unidad de Investigacion, Hospital Son Dureta, Andrea Doria, Palma de Mallorca, 07014,4 and
Venue
Antimicrobial Agents and Chemotherapy
Published
2001-04
Volume
45
Issue
4
Pages
1151-1161
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2061729558
Cited by
1,639
References
75
Citations by year
2026: 41 · 2025: 58 · 2024: 89 · 2023: 84 · 2022: 100 · 2021: 90 · 2020: 107 · 2019: 107 · 2018: 86 · 2017: 82 · 2016: 109 · 2015: 89 · 2014: 100 · 2013: 83 · 2012: 88
FWCI
4.45
Type
journal article
Language
en
Open access
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Enterobacteriaceae and Cronobacter Research
  • Physical Sciences › Environmental Science › Pollution › Pharmaceutical and Antibiotic Environmental Impacts
Keywords
Klebsiella pneumoniae, carbapenemase, carbapenem resistance, beta-lactamase, imipenem, meropenem, extended-spectrum cephalosporins, aztreonam resistance, nonconjugative plasmids, plasmid-mediated gene transfer, clavulanic acid, tazobactam, outer membrane porins, OmpK35, OmpK36
MeSH terms
Meropenem, Amino Acid Sequence, Bacterial Outer Membrane Proteins, Base Sequence, beta-Lactamases, Cloning, Molecular, Escherichia coli, Kinetics, Klebsiella pneumoniae, Microbial Sensitivity Tests, Molecular Sequence Data, Phylogeny, Substrate Specificity, Thienamycins, Transformation, Bacterial, Imipenem, Carbapenems, Sequence Homology, Amino Acid, beta-Lactam Resistance

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