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Genomics identifies source of Klebsiella outbreak

Posted on behalf of Marian Turner

During this year’s German Escherichia coli outbreak, scientists predicted that next-generation whole genome sequencing would soon become the norm for identifying novel human pathogens.

The first test case has arrived. A strain of Klebsiella pneumoniae bacteria is sweeping a Dutch hospital, killing 28 people so far. The Dutch National Institute for Public Health and the Environment (RIVM) yesterday announced a set of genes for specific diagnosis of the strain, developed by scientists who mined the bacterium’s genome.

Dutch media reports that Maasstad hospital in Rotterdam has been reporting K. pneumoniae infections since late 2010. Since then, at least 80 patients have been infected and the hospital estimates that more than 2,000 may have been exposed to the bacteria.

The strain is resistant to many antibiotics, and also contains the gene for Oxa-48, an enzyme that allows it to resist the carpabenem antibiotics typically used to treat broad-spectrum antibiotic Klebsiella. Many exposed patients have been referred to other hospitals or nursing homes throughout the Netherlands, and the RIVM wanted to test these patients to prevent spread of the infection.

Scientists from the University of Münster in Germany and the US-based genome sequencing company Life Technologies sequenced the outbreak strain on an Ion Torrent PGM genome sequencer and assemled a draft sequence. Scientists at the Wellcome Trust Sanger Institute in Cambridge, UK, then compared sections of the genome with 200 Klebsiella genomes in their database and found two regions present only in the outbreak strain.

What these regions do is not known, but one of them forms the basis of a genetic test, together with a gene from Klebsiella and two genes for antibiotic resistance, that the RIVM has now given to Dutch hospitals to screen patients for the bacteria.

“In the E. coli outbreak, we had enough E. coli reference strains and knew enough about E. coli biology to quickly identify a set of genes for specific diagnostics before we had the whole genome sequence,” says Dag Harmsen, a microbiologist at the University of Münster who was involved in sequencing efforts during both outbreaks. “But we don’t have as much experience with Klebsiella, so this time we really needed the whole genome,” he says.

“I think every large hospital will soon have a benchtop whole genome sequencer,” says Harmsen. But rapid science can only help when there is rapid recognition of a threat. The director of the Maasstad hospital, Paul Smits, resigned on 9 August following condemnation of his hospital’s slow response to the outbreak.

Although Oxa-48 resistance is unusual, Oxa-48 resistant K. pneumoniae outbreaks occurred in Turkey in 2010 and France in 2011. Scientists are now comparing the bacterial genomes to see if the same strain has hopped countries.


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