We have recently initiated an investigation of Insertion Sequence movements in multi drug resistant bacteria with a focus on carbapenemase-producing Enterobacteriacaea (CPE). Transposable elements are often associated with antibiotic resistance determinants, suggesting a role in the emergence of resistance. One insertion sequence, IS26, has been reported to be frequently associated with resistance determinants, but its role remained unclear. We have analyzed the genomic contexts of 70 IS26 copies in several clinical and surveillance CPE isolates from the NIH Clinical Center. We used target site duplications (TSDs) and their distribution patterns as guides and discovered that a large fraction of plasmid reorganizations result from IS26 intramolecular replicative transpositions, including replicon fusions, DNA inversions, and deletions. We have now extended these studies to other types of mobile elements. We are also interested in following the ongoing reorganization of plasmids carrying multidrug-resistant determinants from the perspective of their active mobile elements. Curcio, M.J. and Derbyshire, K.M. (2003) Nat. Rev. Mol. Cell. Biol. 4, 865-877. Debets-Ossenkopp, Y.J., et al. (1999) Antimicrob. Agents Chemother. 43, 2657-2662. Sebaihia, M. et al. (2006) Nature Genet. 38, 779-786.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2015
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
Zip Code
Morero, Natalia RosalĂ­a; Zuliani, Cecilia; Kumar, Banushree et al. (2018) Targeting IS608 transposon integration to highly specific sequences by structure-based transposon engineering. Nucleic Acids Res 46:4152-4163
Snesrud, Erik; He, Susu; Chandler, Michael et al. (2016) A Model for Transposition of the Colistin Resistance Gene mcr-1 by ISApl1. Antimicrob Agents Chemother 60:6973-6976
He, Susu; Chandler, Michael; Varani, Alessandro M et al. (2016) Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids. MBio 7:
Hickman, Alison B; Dyda, Fred (2016) DNA Transposition at Work. Chem Rev :
He, Susu; Hickman, Alison Burgess; Varani, Alessandro M et al. (2015) Insertion Sequence IS26 Reorganizes Plasmids in Clinically Isolated Multidrug-Resistant Bacteria by Replicative Transposition. MBio 6:e00762
Hickman, Alison B; Dyda, Fred (2015) Mechanisms of DNA Transposition. Microbiol Spectr 3:MDNA3-0034-2014
Hickman, Alison B; Dyda, Fred (2014) CRISPR-Cas immunity and mobile DNA: a new superfamily of DNA transposons encoding a Cas1 endonuclease. Mob DNA 5:23
He, Susu; Guynet, Catherine; Siguier, Patricia et al. (2013) IS200/IS605 family single-strand transposition: mechanism of IS608 strand transfer. Nucleic Acids Res 41:3302-13
Chandler, Michael; de la Cruz, Fernando; Dyda, Fred et al. (2013) Breaking and joining single-stranded DNA: the HUH endonuclease superfamily. Nat Rev Microbiol 11:525-38
Messing, Simon A J; Ton-Hoang, Bao; Hickman, Alison B et al. (2012) The processing of repetitive extragenic palindromes: the structure of a repetitive extragenic palindrome bound to its associated nuclease. Nucleic Acids Res 40:9964-79

Showing the most recent 10 out of 17 publications