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Insertion Sequence IS26 Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative
Susu He1, Alison Burgess Hickman1, Alessandro M Varani2
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Mbio
|June 11, 2015
Summary
Replicative transposition by IS26 drives plasmid reorganization in carbapenemase-producing Enterobacteriaceae (CPE). This mechanism explains the evolution of extreme drug resistance and has clinical implications.
Area of Science:
- Molecular Biology
- Microbiology
- Genetics
Background:
- Carbapenemase-producing Enterobacteriaceae (CPE) pose a global health threat due to multidrug resistance.
- Transposable elements, like IS26, are implicated in the emergence of antibiotic resistance.
- The precise role and transposition mechanism of IS26 in resistance plasmids remained unclear.
Purpose of the Study:
- To investigate the transposition mechanism of IS26 in clinical CPE isolates.
- To elucidate the role of IS26 in the genomic reorganization of resistance plasmids.
- To understand the evolution of extreme drug resistance phenotypes.
Main Methods:
- Analysis of genomic contexts of IS26 copies in CPE isolates.
- Utilizing target site duplication (TSD) patterns to infer transposition events.
- Examining plasmid reorganizations including fusions, inversions, and deletions.
Main Results:
- IS26 predominantly utilizes replicative transposition.
- Replicative transposition by IS26 drives significant plasmid reorganization (fusions, inversions, deletions).
- Transposon Tn4401, carrying the blaKPC gene, also likely employs replicative transposition.
Conclusions:
- Replicative transposition is a key driver of plasmid evolution in multidrug-resistant bacteria.
- Understanding IS26 transposition provides insights into the spread of antibiotic resistance.
- This study offers a method to trace resistance plasmid evolution using TSD patterns.
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