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In Texas, New View of Klebsiella Strain Diversity and Antibiotic Resistance

Friday, June 2, 2017

A sweeping new report on Klebsiella pneumoniae sequence data from scientists at the Houston Methodist Research Institute, Weill Cornell Medical College, and other institutions found more diversity than expected in strains of the pathogen in a Texas population. The publication also indicates the emergence of a virulent, antibiotic-resistant strain of this organism.

Published in mBio, “Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307” comes from lead author Wesley Long, senior author James Musser, and collaborators.

K. pneumoniae is a dangerous source of infection, often acquired in hospitals and increasingly resistant to antibiotics. Scientists launched this study to contribute new genomic information that might be used to inform new therapeutics. They sequenced nearly 1,800 isolates collected from patients in the Houston Methodist Hospital system over four years, and then selected five key strains for deeper analysis with SMRT Sequencing.

Previous Klebsiella studies in the U.S. had determined that clonal group 258 was dominant in this country. In this project, however, scientists found that this group represented just a quarter of isolates. More than 35% of strains belonged to clonal group 307, with isolates collected in a number of hospitals. The remaining cases represented a number of different strain types. “We discovered that CG307 strains have been abundant in Houston for many years,” the scientists report, noting that this strain is as virulent as pandemic K. pneumoniae strains. “Our results may portend the emergence of an especially successful clonal group of antibiotic-resistant K. pneumoniae.”

The team used SMRT Sequencing to generate reference-grade genome assemblies and annotations for five strains “chosen to represent regions of the phylogenetic tree for which existing reference genomes deposited in [publicly] available databases were lacking,” the authors report. “In addition, genomes containing the blaNDM-1 and OXA-48 genes… were chosen to allow more in-depth analysis of these important strains.”

All five strains were represented in closed genome assemblies, with two to five plasmids for each. Analysis revealed that a reference strain previously collected in Pittsburgh and one of the Houston isolates “are lineally descended from a common ancestor organism,” the scientists write.

Sequencing efforts were followed up with transcriptome analysis and mouse models to produce data that could be relevant for the development of new therapies. The team also used the whole genome data to generate “classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested,” they write. “We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research.”

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