Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains
Abstract Background Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Genome Medicine |
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| Online Access: | https://doi.org/10.1186/s13073-023-01153-y |
| _version_ | 1797945809996611584 |
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| author | Anton Spadar João Perdigão Susana Campino Taane G. Clark |
| author_facet | Anton Spadar João Perdigão Susana Campino Taane G. Clark |
| author_sort | Anton Spadar |
| collection | DOAJ |
| description | Abstract Background Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden in other geographical regions. Methods Here, we examined the largest collection of publicly available sequenced Kp isolates (n=13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp. Results We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp (n=1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones. Conclusions Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally. |
| first_indexed | 2024-04-10T21:01:00Z |
| format | Article |
| id | doaj.art-74697a26a2434d4e87661ec1dbcb2c77 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-04-10T21:01:00Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-74697a26a2434d4e87661ec1dbcb2c772023-01-22T12:20:52ZengBMCGenome Medicine1756-994X2023-01-0115111210.1186/s13073-023-01153-yLarge-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strainsAnton Spadar0João Perdigão1Susana Campino2Taane G. Clark3Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineResearch Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de LisboaFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineAbstract Background Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden in other geographical regions. Methods Here, we examined the largest collection of publicly available sequenced Kp isolates (n=13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp. Results We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp (n=1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones. Conclusions Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally.https://doi.org/10.1186/s13073-023-01153-yAMRCarbapenemHypervirulenceKlebsiella |
| spellingShingle | Anton Spadar João Perdigão Susana Campino Taane G. Clark Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains Genome Medicine AMR Carbapenem Hypervirulence Klebsiella |
| title | Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| title_full | Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| title_fullStr | Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| title_full_unstemmed | Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| title_short | Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains |
| title_sort | large scale genomic analysis of global klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem resistant hypervirulent strains |
| topic | AMR Carbapenem Hypervirulence Klebsiella |
| url | https://doi.org/10.1186/s13073-023-01153-y |
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