Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime–Avibactam in an ST11 Klebsiella pneumoniae Strain
Abstract
:1. Introduction
2. Materials and Methods
2.1. The Strains and In Vitro Susceptibility
2.2. Whole Genome Sequencing and Analysis
2.3. qRT-PCR
2.4. Cloning Experiment
2.5. Kinetic Assay and Determination of IC50 Values
2.6. Structure Prediction
2.7. Comparative Secondary and Stereoscopic Structures
2.8. Molecular Docking
2.9. Mating Experiments
3. Results
3.1. Antimicrobial Susceptibility
3.2. Genomic Analysis of Clinical K. pneumoniae Isolate 130125
3.3. Genetic Context of blaKPC-204-Carrying Plasmid
3.4. Relative blaKPC Gene’s Expression Levels
3.5. Identification of blaKPC-204 Involved in CZA Resistance
3.6. Enzyme Kinetic Parameters and IC50 Values
3.7. Comparative Secondary and Stereoscopic Structures of KPC-204 and Related Variants
3.8. Molecular Docking of KPC-204 and KPC-2 with Ceftazidime, Avibactam and Meropenem
3.9. blaKPC-204 Was Located in a Self-Transmissible Plasmid
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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MICs (mg/L) a | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Strains | PIP | TZP | FOX | FEP | ATM | CAZ | CZA | IPM | IMR | MEM | MEV | ETP |
130125 | >512 | 256 | >512 | >512 | 512 | >512 | 256 | 64 | 0.25 | 64 | 0.5 | 64 |
015093 | >512 | >512 | >512 | >512 | 512 | >512 | 0.5 | 128 | 0.25 | 256 | 0.06 | 64 |
DH5α::pEKPC-2 | >512 | >512 | >512 | >512 | 512 | 128 | 0.5 | 16 | 0.125 | 8 | 0.03 | 8 |
DH5α::pEKPC-204 | >512 | 256 | >512 | 512 | 256 | 128 | 64 | 16 | 0.125 | 16 | 0.125 | 8 |
DH5α::pET28a | 1 | 1 | 2 | 0.06 | 0.125 | 0.25 | 0.25 | 0.25 | 0.06 | ≤0.015 | ≤0.015 | ≤0.015 |
E. coli J53 | 1 | 1 | 1 | 0.06 | 0.125 | 0.25 | 0.125 | 0.125 | 0.06 | ≤0.015 | ≤0.015 | ≤0.015 |
J53::pKPC2_015093 | >512 | >512 | >512 | 512 | 512 | 512 | 0.5 | 32 | 0.25 | 32 | 0.03 | 32 |
J53::KPC204_130125 | >512 | 256 | >512 | 512 | 512 | 512 | 64 | 32 | 0.25 | 64 | 0.25 | 32 |
Accession No. | Size, bp | Replicon Type | Resistance Genes | ||
---|---|---|---|---|---|
β-Lactam | Other | ||||
130125_chr | CP148996 | 5,462,753 | - | blaSHV-158 | aadA2, fosA6 |
pKPC204_130125 | CP148997 | 154,728 | IncR, IncFII | blaKPC-204, blaTEM-1, blaCTX-M-65 | rmtB1 |
p1_130125 | CP148998 | 10,060 | ColRNAI | ||
p2_130125 | CP148999 | 5596 | - |
KPC-2 | KPC-204 | |||||
---|---|---|---|---|---|---|
β-Lactam | Km (μM) | kcat (s−1) | kcat/Km (μM−1·s−1) | Km (μM) | kcat (s−1) | kcat/Km (μM−1·s−1) |
Nitrocefin | 22.124 | 97.589 | 4.411 | 31.178 | 116.419 | 3.734 |
Ceftazidime | 870.413 | 5.226 | 0.006 | 975.154 | 7.801 | 0.008 |
Meropenem | 15.283 | 5.194 | 0.34 | 14.157 | 8.325 | 0.588 |
IC50 (μM) | ||
---|---|---|
Inhibitor | KPC-2 | KPC-204 |
Avibactam | 0.045 | 0.569 |
Tazobactam | 1.782 | 0.083 |
Clavulanic acid | 0.887 | 0.124 |
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Gong, Y.; Feng, Y.; Lv, X. Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime–Avibactam in an ST11 Klebsiella pneumoniae Strain. Microorganisms 2024, 12, 1193. https://doi.org/10.3390/microorganisms12061193
Gong Y, Feng Y, Lv X. Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime–Avibactam in an ST11 Klebsiella pneumoniae Strain. Microorganisms. 2024; 12(6):1193. https://doi.org/10.3390/microorganisms12061193
Chicago/Turabian StyleGong, Yanqiao, Yu Feng, and Xiaoju Lv. 2024. "Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime–Avibactam in an ST11 Klebsiella pneumoniae Strain" Microorganisms 12, no. 6: 1193. https://doi.org/10.3390/microorganisms12061193