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Genomic Analysis Traces Transplant Recipient Infection Back to Donor

NEW YORK (GenomeWeb) – A new genomic analysis suggests that a form of vancomycin-resistant Enterococcus (VRE) may be transmitted from organ donors to recipients via the transplanted organs.

Researchers from Mount Sinai's Icahn School of Medicine, the University of Texas Medical School, and the non-profit organ procurement organization LiveOnNY used pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and whole-genome sequencing to characterize VRE isolates linked to bloodstream and surgical site infections in a 65-year-old liver transplant recipient.

The team's findings, published yesterday in PLOS One, indicated that the man's bloodstream infection was caused by a form of VRE that was almost genetically identical to a strain detected in the deceased 51-year-old woman who donated the liver.

The researchers employed "multiple genomics strategies, culminating in WGS, to demonstrate donor acquisition of VRE in a liver transplant recipient with surgical site and bloodstream infection by comparing donor and recipient genomes with contemporary hospital isolates," senior author Shirish Huprikar, an infectious diseases researcher at Mount Sinai, and his co-authors wrote.

It can be difficult to discern between organ-transmitted microbial infections and infections that organ recipients pick up in the hospital setting over the course of their treatment, the team noted. But the availability of affordable genome sequencing methods is expected to make it more straightforward to tease apart infection sources in general, including infections acquired by organ transplant recipients.

Indeed, authors of the new study noted that "WGS may be increasingly necessary to unambiguously confirm transmission for structurally mutable genomes."

For their part, the researchers focused on an infection affecting a recent liver transplant recipient, who had received blood transfusions and treatment for acute post-transplant kidney problems. By culturing blood samples collected in the days after his liver transplant, they identified VRE and Candida yeast in the organ recipient samples.

After initial PFGE and MLST analyses demonstrated strong similarities between VRE isolates obtained from the liver transplant recipient and donor, the team went on to do sequencing and de novo genome assembly on VRE isolates with reads generated on the Pacific Biosciences RS II platform.

The researchers also used Illumina HiSeq 2500 instruments to re-sequence the genomes of liver donor VRE, the recipient VRE, and a handful of other VRE isolates. Their phylogenetic analysis, which included a dozen VRE genomes, indicated that isolates from the liver donor and recipient fell in the same sub-clade, typed as ST736 by MLST.

In general, the liver donor and recipient VRE isolates shared SNP patterns, though the team detected some structural differences between them, particularly insertions and deletions falling at several sites in the genome. Even so, the genomic profiles were more consistent with donor-to-recipient transmission of the VRE than with infection from another hospital source.

"Comparison of de novo assembled isolate genomes was highly suggestive of transplant transmission rather than hospital-acquired transmission," Huprikar and co-authors wrote, "and also identified subtle internal rearrangements between donor and recipient missed by other genomic approaches."