International Team Publishes Comprehensive DNA
Analysis of Outbreak Strain and 11 Related Strains in
Journal of Medicine
An international team of scientists has successfully employed single
molecule, real-time (SMRT™) DNA sequencing technology from
Biosciences of California, Inc. (NASDAQ:PACB) to provide valuable
insights into the pathogenicity and evolutionary origins of the highly
virulent bacterium responsible for the German E. coli outbreak.
Published online today in the
results provide the most detailed genetic profile to date of the
outbreak strain, including medically relevant information.
The researchers determined the outbreak strain was a member of the
enteroaggregative pathotype of E. coli (EAEC) with serotype
O104:H4. The outbreak isolates are distinguished from other O104:H4
strains because they contain genes encoding
distinct set of additional virulence and antibiotic resistance factors.
In addition, the team found that expression of the stx2 gene was
increased by certain antibiotics including ciprofloxacin, suggesting
caution should be used before using certain classes of antibiotics to
counteract this newly emerged pathogen.
By sequencing the outbreak strain and 11 related strains with the PacBio RS,
the team concluded that horizontal genetic exchange with the
toxin-producing enterohemorrhagic E. coli (EHEC) strain enabled
the emergence of the highly virulent
strain. The genetic analysis also indicates that evolution of this new
form was a relatively recent event.
The team identified many virulence factor genes commonly found in EAEC.
Furthermore, the exceptionally long sequencing reads that are
characteristic of PacBio SMRT DNA sequencing technology enabled the team
to also detect larger-scale deletions, insertions, inversions and other
structural variation between the O104:H4 outbreak samples and the other
O104:H4 EAEC samples that were sequenced. Several of these structurally
divergent regions house genes that encode virulence factors. Another
feature in which the current outbreak diverges from common EAEC isolates
is in the number and nature of SPATE proteases. Taken together, the
results provide a possible explanation for the increased virulence of
the German E. coli outbreak strain.
The authors included scientists in the U.S. and
Biosciences, the
Collaborating Centre for Reference and Research on Escherichia coli
and Klebsiella, the Statens Serum Institut,
Hospital, Brigham and Women’s Hospital and
“This multi-strain sequencing data and analysis significantly increases
the amount of scientific information available for the study of this new
deadly form of E. coli and has yielded critical insights into its
causative agent,” said co-author,
Professor,
Genome Sciences and
results provide the most complete published genome of this strain to
date and highlight the importance of DNA sequencing to understanding how
the plasticity of bacterial genomes facilitates the emergence of new
pathogens.”
Whole genome sequencing involves decoding the precise order of
nucleotide bases that make up an organism’s complete set of DNA and
provides more comprehensive information than other analysis methods such
as DNA fingerprinting or arrays. With advances in technology and
decreasing cost, whole genome sequencing is emerging as the gold
standard method for identifying and classifying infectious agents. SMRT
technology is the latest advance in DNA sequencing, capable of
generating long sequence reads to resolve structural variations and
complex genomes at ultra-fast speeds by ‘eavesdropping’ on DNA
replicating in real time.
co-author of the paper commented: “We have reached a new era in which
communities of researchers can rapidly share large-scale data sets and
analyses vital for public health. Sequencing genomes in hours, as
opposed to days or weeks, with unprecedented read lengths is the
emerging hallmark of third generation DNA sequencing. The long PacBio RS
reads enabled a PacBio-only de novo genome assembly, a key
component of new pathogen characterization, as well as deeper insights
into structural variants.”
The paper is available at www.nejm.com.
The data are available for the bioinformatics community at the PacBio
developer’s network (DevNet) web site (www.pacbiodevnet.com),
where a suite of open source tools and other resources designed for SMRT
sequence data are available to analyze the information. A summary of the
sequencing project appears on the Pacific Biosciences website at https://blog.pacificbiosciences.com.
More information about SMRT technology is available at www.pacificbiosciences.com.
About Pacific Biosciences
Pacific Biosciences’ mission is to transform the way humankind acquires,
processes and interprets data from living systems through the design,
development and commercialization of innovative tools for biological
research. The company has developed a novel approach to studying the
synthesis and regulation of DNA, RNA and proteins. Combining recent
advances in nanofabrication, biochemistry, molecular biology, surface
chemistry and optics, Pacific Biosciences has created a powerful
technology platform called single molecule, real-time, or SMRT™,
technology. SMRT technology enables real-time analysis of biomolecules
with single molecule resolution, which has the potential to transform
the understanding of biological systems by providing a window into these
systems that has not previously been open for scientific study.
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recently filed Quarterly Report on Form 10-Q. All forward-looking
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For Pacific Biosciences
nicole@bioscribe.com
or
Pacific
Biosciences
ir@pacificbiosciences.com
Source: Pacific Biosciences
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