March 3, 2017  |  General

‘Mobilome’ Study of Antibiotic Resistance Implicates Transposon Activity

Klebsiella pneumoniae
Klebsiella pneumoniae

A recent effort to understand the genetic mechanisms behind swappable elements of drug-resistance among bacteria built on previous studies of Enterobacteriaceae isolates collected at the National Institutes of Health Clinical Center. The work was made possible by high-quality genome assemblies of these organisms generated earlier with SMRT Sequencing technology.
In this project, scientists from the U.S., France, and Brazil teamed up to learn precisely how drug-resistance plasmids are spread from one species to another. They report the results of that investigation in mBio with the publication “Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids” from lead author Susu He, senior author Fred Dyda, and collaborators. The team focused on the full complement of mobile elements (or the “mobilome”) found in carbapenemase-producing Enterobacteriaceae. “The availability of highly accurate plasmid assemblies for these strains based on long-read PacBio SMRT sequencing allows for the unambiguous and precise annotation of mobile elements,” they report.
The scientists analyzed plasmid evolution from isolates collected during an outbreak of carbapenem-resistant Klebsiella pneumoniae at the NIH Clinical Center in 2011 and 2012 as well as from other samples collected at the center over several years. By tracking target site duplications in samples, the team could infer the evolution of drug resistance. “We are able to propose the exact historical molecular events underlying plasmid rearrangements which provide a basis for understanding how antibiotic-resistant strains change over time, with significant implications for combating plasmid-mediated antimicrobial resistance,” they write.
Of course, that raises the question of which evolutionary mechanisms are causing the changes they characterized. The scientists found two mobile element types — IS26 and Tn3 transposons — that appeared to be driving drug resistance evolution in the K. pneumoniae samples studied. However, they note, there was no clear explanation for that discovery. “This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination,” the authors report, adding that perhaps this kind of information will one day inform new approaches to combat antibiotic resistance.
“The rapidly decreasing cost of high-quality, long-read sequencing will enable the type of analysis described here to be applied more broadly to the problem of how resistance plasmids evolve in patients, hospitals, and the environment,” the scientists conclude.
Now, with the Sequel System and the recently released protocols for multiplexed microbial genome assembly, this application is even more accessible for the scientific community.

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