Single Molecule, Real-Time (SMRT) DNA Sequencing Tracks Infectious Disease Pathogens More Effectively Than Short-Read Technologies
Wednesday, September 17, 2014
Today in Science Translational Medicine1, researchers from the
Carbapenem-resistant Enterobacteriaceae (CRE) are associated with a 40%-80% mortality rate from infection according to published studies. Further, the incidence of CRE in the US has quadrupled over the past decade and has been found in nearly every state, including nearly 20% of long-term acute care facilities housing some of the most vulnerable patients. “In the face of a dwindling selection of drugs to fight healthcare-associated infections, prevention is critical. In addition to implementing recommended infection control measures such as surveillance, hand hygiene, and barrier precautions, we must find more sophisticated methods to detect, track and eradicate multidrug-resistant bacteria,” the authors write.
After an outbreak in the NIH Clinical Center in 2011, NHGRI researchers sought to survey and better understand the issue of plasmid “trafficking” in the hospital setting where the environment, patients, and healthcare personnel may each serve as reservoirs. The researchers used SMRT Sequencing to identify and track plasmids within bacterial isolates, revealing a complex pattern of introduction and environmental spread of carbapenemase-encoding plasmids.
Because plasmid sequences contain complexities such as repeats and mobile genetic elements, previous attempts to sequence them with short-read technology were not able to discriminate and resolve plasmid from chromosomal genes. The highly accurate, fully contiguous genome sequence data provided by SMRT Sequencing, including full plasmid identification, challenge previous assumptions about horizontal gene transfer events within patients and point to the possibility of environmental connections.
The results have great implications for allocation of hospital infection control resources. “Given the limited resources in all health care facilities, sequence data can help focus and direct the use of allotted funds for infection control interventions, thus providing the best patient care,” the researchers concluded.
Today’s paper follows several other papers describing the benefits of SMRT Sequencing for infectious disease applications. In one report2, researchers from the University of
In another study3,
In a report4 published earlier this month, researchers from
transmission and/or ability to cause disease in M. catarrhalis-based infections. SMRT technology is the only sequencing technology available that offers detection of base modications as part of the sequencing process.
“SMRT Sequencing has emerged as the gold standard in microbial sequencing for its ability to close genomes into a single contig, resolve plasmids, and detect base modifications such as methylation,” said
Non-microbial infectious disease research has benefited from SMRT Sequencing, as well. A recent paper5 from researchers at the
2Doi et al. (2014) Whole genome assembly of Klebsiella pneumoniae co-producing NDM-1 and OXA-232 carbapenemases using Single-Molecule, Real-Time Sequencing. Antimicrobial Agents and Chemotherapy doi: 10.1128/AAC.03180-14.
3Katrin et al. (2014) A novel Tn3-like composite transposon harboring blaVIM-1 in Klebsiella pneumoniae spp. pneumoniae isolated from river water. Microbial Drug Resistance doi: 10.1089/mdr.2014.0055.
4Blakeway et al. (2014) ModM DNA methyltransferase methylome analysis reveals a potential role for Moraxella catarrhalis phasevarions in otitis media.
5Tallon et al. (2014) Single molecule sequencing and genome assembly of a clinical specimen of Loa loa, the causative agent of loiasis. BMC Genomics 15: 788.
About the PacBio RS II and SMRT Sequencing
Pacific Biosciences’ SMRT Sequencing technology achieves the industry’s longest read lengths, highest consensus accuracy and the least degree of bias. These characteristics, combined with the ability to detect many types of DNA base modifications (e.g., methylation) as part of the sequencing process, make the PacBio RS II an essential tool for many scientists studying genetic and genomic variation. The PacBio platform provides a sequencing solution that can address a growing number of complex medical, agricultural and industrial problems.
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