Genomic Analysis of Carbapenemase-Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethical Approval
2.2. Study Site and Sample Collection
2.3. Isolation and Identification of Carbapenemase-Producing Klebsiella Pneumoniae Isolates
2.3.1. Culture Screening Methods
2.3.2. Detection and Identification of CPE Colonies
2.4. Antibiotic Susceptibility Testing (AST)
2.5. DNA Extraction Genome Sequencing and Analysis
2.6. WGS-Based Confirmation and Molecular Typing of K. Pneumoniae Isolates
2.7. WGS Identification of the Acquired and Chromosomal Mutations in the Isolates
2.8. WGS Identification of Mobile Genetic Elements (MGEs)/Genetic Support
2.9. Phylogenomic Analyses of the K. Pneumoniae Isolates (n = 10)
2.10. Accession Numbers
3. Results
3.1. Identification, Confirmation and Phenotypic Analysis
3.2. Genomic Confirmation and Resistance Profiling of β-Lactamases
3.3. WGS-Based Capsular Serotyping and Multilocus Sequence Typing (MLST)
3.4. WGS Detection of Carbapenemase-Encoding BlaNDM-1 Plasmid Involved in Horizontal Spread
3.5. Phylogenomic Insights
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Bacterial Isolate * | MIC (mg/L) † | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
No. | Strain ID | Category | IMP | MEM | FEP | CXM | CTX | CAZ | CRO | FOX | AMP | AMC | TZP | AMX | GEN | AMK | CIP | ERT | SXT | TGC |
1 | B1 | XDR | ≥16 | ≥16 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | ≤0.5 |
2 | B2 | XDR | ≥16 | ≥16 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 2 |
3 | B3 | XDR | ≥16 | ≥16 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 1 |
4 | B4 | XDR | ≥16 | ≥16 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 2 |
5 | B5 | XDR | ≥16 | ≥16 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 2 |
6 | R1 | XDR | ≥16 | ≥16 | 32 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 1 |
7 | R2 | XDR | ≥16 | ≥16 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | ≤0.5 |
8 | R3 | XDR | ≥16 | ≥16 | 32 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 2 |
9 | R4 | XDR | ≥16 | ≥16 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 1 |
10 | R5 | XDR | ≥16 | ≥16 | 32 | ≥64 | ≥64 | ≥64 | ≥64 | ≥64 | ≥32 | ≥32 | ≥128 | ≥32 | ≥16 | ≥64 | ≥4 | ≥8 | ≥320 | 1 |
Isolate * | Patient’s | Isolate’s | Carba NP † | β-Lactamase Genes | In-Silico Typing | |||||
---|---|---|---|---|---|---|---|---|---|---|
No. | Strain ID | Sex | Age (Years) | Date | Source | MLST | K Typing | Allelic Types | ||
1 | B1 | M ‡ | 24 | 15/04/2017 | Blood | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
2 | B2 | F § | 14 | 29/01/2017 | Blood | + | NDM-1, ---------, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
3 | B3 | M | 30 | 03/01/2017 | Blood | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
4 | B4 | M | 15 days | 21/03/2017 | Blood | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
5 | B5 | - | 8 months | 25/04/2017 | Blood | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
6 | R1 | F | 61 | 20/05/2016 | Rectal | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST3136 | KL149 | wzc:928, wzi:110 |
7 | R2 | F | 72 | 18/07/2016 | Rectal | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
8 | R3 | M | 25 | 13/06/2016 | Rectal | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
9 | R4 | F | 21 | 11/07/2016 | Rectal | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
10 | R5 | F | 66 | 27/07/2016 | Rectal | + | NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1 | ST152 | KL149 | wzc:928, wzi:110 |
Bacterial Strain | Carbapenemase 1 | Plasmids Structure 2 (% Identity) 3 | Plasmid Replicon Types | Plasmid MLST (Pmlsts) | Insertion Sequences | Intact Prophage | |
---|---|---|---|---|---|---|---|
No. | ID | ||||||
1 | B1 | NDM-1:bleMBL | p18-43_01-like [100%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI | IncF[K12:A-:B36] | IS6, ISL3, IS256, IS3 | 10 |
2 | B2 | NDM-1:bleMBL | p18-43_01-like [99%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI | IncF[K12:A-:B36] | IS1182, IS5, ISNCY, ISL3 | 10 |
3 | B3 | NDM-1:bleMBL | p18-43_01-like [99%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI | IncF[K12:A-:B36] | IS6, ISL3, IS256, IS3 | 10 |
4 | B4 | NDM-1:bleMBL | p18-43_01-like [100%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI, Col440I | IncF[K12:A-:B36] | ISL3, IS256, IS481, IS21 | 10 |
5 | B5 | NDM-1:bleMBL | p18-43_01-like [100%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI, Col440I | IncF[K12:A-:B36] | IS6, IS66, IS1182, ISL3 | 10 |
6 | R1 | NDM-1:bleMBL | p18-43_01-like [100%] | IncFIB(K), IncFII, IncFIB(pB171),IncFII(Yp), ColRNAI | IncF[K12:A-:B36] | IS6, ISL3, IS256, IS3 | 10 |
7 | R2 | NDM-1:bleMBL | p18-43_01-like [99%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp),ColRNAI | IncF[K12:A-:B36] | IS6, IS66, IS1182, ISL3 | 10 |
8 | R3 | NDM-1:bleMBL | p18-43_01-like [99%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI, Col440I | IncF[K12:A-:B36] | IS6, IS66, IS1182, ISL3 | 10 |
9 | R4 | NDM-1:bleMBL | p18-43_01-like [100%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI | IncF[K12:A-:B36] | IS1595, ISLre2, IS5, IS4 | 10 |
10 | R5 | NDM-1:bleMBL | p18-43_01-like [100%] | IncFIB(K), IncFII, IncFIB(pB171), IncFII(Yp), ColRNAI | IncF[K12:A-:B36] | IS6, ISL3, IS256, IS3 | 10 |
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Ramsamy, Y.; Mlisana, K.P.; Allam, M.; Amoako, D.G.; Abia, A.L.K.; Ismail, A.; Singh, R.; Kisten, T.; Swe Han, K.S.; Muckart, D.J.J.; et al. Genomic Analysis of Carbapenemase-Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa. Microorganisms 2020, 8, 137. https://doi.org/10.3390/microorganisms8010137
Ramsamy Y, Mlisana KP, Allam M, Amoako DG, Abia ALK, Ismail A, Singh R, Kisten T, Swe Han KS, Muckart DJJ, et al. Genomic Analysis of Carbapenemase-Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa. Microorganisms. 2020; 8(1):137. https://doi.org/10.3390/microorganisms8010137
Chicago/Turabian StyleRamsamy, Yogandree, Koleka P. Mlisana, Mushal Allam, Daniel G. Amoako, Akebe L. K. Abia, Arshad Ismail, Ravesh Singh, Theroshnie Kisten, Khine Swe Swe Han, David J. Jackson Muckart, and et al. 2020. "Genomic Analysis of Carbapenemase-Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa" Microorganisms 8, no. 1: 137. https://doi.org/10.3390/microorganisms8010137