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Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene bla KPC
Open accessAbstract
The recent widespread emergence of carbapenem resistance in Enterobacteriaceae is a major public health concern, as carbapenems are a therapy of last resort against this family of common bacterial pathogens. Resistance genes can mobilize via various mechanisms, including conjugation and transposition; however, the importance of this mobility in short-term evolution, such as within nosocomial outbreaks, is unknown. Using a combination of short- and long-read whole-genome sequencing of 281 bla KPC -positive Enterobacteriaceae isolates from a single hospital over 5 years, we demonstrate rapid dissemination of this carbapenem resistance gene to multiple species, strains, and plasmids. Mobility of bla KPC occurs at multiple nested genetic levels, with transmission of bla KPC strains between individuals, frequent transfer of bla KPC plasmids between strains/species, and frequent transposition of bla KPC transposon Tn 4401 between plasmids. We also identify a common insertion site for Tn 4401 within various Tn 2 -like elements, suggesting that homologous recombination between Tn 2 -like elements has enhanced the spread of Tn 4401 between different plasmid vectors. Furthermore, while short-read sequencing has known limitations for plasmid assembly, various studies have attempted to overcome this by the use of reference-based methods. We also demonstrate that, as a consequence of the genetic mobility observed in this study, plasmid structures can be extremely dynamic, and therefore these reference-based methods, as well as traditional partial typing methods, can produce very misleading conclusions. Overall, our findings demonstrate that nonclonal resistance gene dissemination can be extremely rapid, presenting significant challenges for public health surveillance and achieving effective control of antibiotic resistance.
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Cites
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Cited by
Mobile Genetic Elements Associated with Antimicrobial Resistance
Partridge, S. R., Kwong, S. M., Firth, N., & Jensen, S. O. (2018) · Clinical Microbiology Reviews · doi:10.1128/cmr.00088-17 · Cited by 2,751
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The Ecology and Evolution of Pangenomes
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Exploring phytochemicals for combating antibiotic resistance in microbial pathogens
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Metadata
- Authors
- Sheppard, A. E., Stoesser, N., Wilson, D. J., Sebra, R., Kasarskis, A., Anson, L. W., Giess, A., Pankhurst, L. J., Vaughan, A., Grim, C. J., Cox, H. L., Yeh, A. J., the Modernising Medical Microbiology (MMM) Informatics Group, Sifri, C. D., Walker, A. S., Peto, T. E., Crook, D. W., & Mathers, A. J.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2016-06
- Volume
- 60
- Issue
- 6
- Pages
- 3767-3778
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- OpenAlex
- W2318209259
- Cited by
- 295
- References
- 44
- FWCI
- 13.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Sheppard, A. E., Stoesser, N., Wilson, D. J., Sebra, R., Kasarskis, A., Anson, L. W., Giess, A., Pankhurst, L. J., Vaughan, A., Grim, C. J., Cox, H. L., Yeh, A. J., the Modernising Medical Microbiology (MMM) Informatics Group, Sifri, C. D., Walker, A. S., Peto, T. E., Crook, D. W., & Mathers, A. J. (2016). Nested Russian Doll-Like Genetic Mobility Drives Rapid Dissemination of the Carbapenem Resistance Gene bla KPC. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.00464-16
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
