Whole genome sequencing may help officials get a handle on disease outbreaks

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Whole genome sequencing may help officials get a handle on disease outbreaks

According to a team of researchers, genome-wide sequencing technology could provide epidemiologists and health workers with a powerful weapon to monitor and eventually control outbreaks of serious diseases.

In one study, researchers found that international and domestic sources of Shigella sonnei, the fourth most common cause of foodborne bacterial disease in the United States, came from a related group of bacteria called Lineage II. The experts initially proposed that the international and national strains of Shigella probably came from different sources, according to the researchers, who published their findings in a recent issue of Microbial Genomics.

"One of the questions we asked was, genetically, whether domestic Shigella are different from those from abroad and, ultimately, the answer was, no, they are not distinct - there doesn't seem to be any stratification based on genetic kinship," said Edward Dudley, Professor of Food Science at Penn State and Associate of the Institute for CyberScience, which gives Penn State researchers access to supercomputer resources.

Since different strains of Shigella may require some treatment, identifying the right type of Shigella at the right time could give public health officials a head start in informing the public about the outbreak and alerting medical staff about the best treatment options, according to Dudley, who is also director of the E. coli Reference Centre and associated with the Huck Institutes of Life Sciences at Penn State. Comparing Shigella samples during an outbreak could also allow health officials to identify possible sources of the disease, monitor its progress and alert officials in areas that may be on the outbreak's trajectory.

"In this study, with this particular species of Shigella, we knew there were five different lines and we identified signatures in the genomes of these organisms that allow us to very quickly tell which of these five species it segregates into," said Dudley. "This helps the Department of Health not only to show how it can use all of the genome technology for research, but perhaps even how it can use it to develop a new diagnostic tool.

Shigella, which causes severe diarrhea and stomach discomfort, usually passes through the stool. Since infected swimmers in public pools and swimming areas are often a frequent source of Shigella outbreaks, the sooner they are alerted of a possible outbreak, the sooner they can take preventive measures and give warnings.

Sequencing the entire genome can determine the complete genome of an organism, including the chromosomal DNA and mitochondrial DNA of the organism. According to Dudley, sequencing the entire genome is faster and more accurate than pulsed field gel electrophoresis, or PFGE, the old standard test that offered only a basic genetic fingerprint of bacteria.

"DNA sequencing data is much clearer to look at - the SESGP is more model-based - and it's much more accurate," said Mr. Dudley. "If you sequence the genome of the bacteria, you now have 5.5 million data points. If there is a perfect match between the food and the patient, then there is no doubt that there is a relationship between the two."

The analysis of the entire genome gives results in just over a day, which is much faster than the IEG. As computer technology advances, Dudley expects the speed of sequencing to increase, which could yield results in a matter of hours.

In an earlier study, Dudley's laboratory in Penn State also used the whole genome analysis to study Salmonella, one of the leading causes of foodborne illness in the United States, which causes about 450 deaths per year and is often associated with contaminated meat sold at retail. In an article published in Microbiology, the researchers stated that salmonella collected from humans was genetically distinct from types collected from meat, such as ground turkey, pork chops and chicken breasts.

"Using the IEG method, the Pennsylvania Department of Health concluded that human and meat isolates were identical," said Dudley. "However, we could show them using the sequencing of the entire genome which - not so fast - you can distinguish them with this new method. So from there, we could support the argument that these people were not getting sick from meat contaminated with these particular strains."

The researchers used sequencing equipment at Penn State. For Shigella, researchers sequenced a total of 22 isolated samples of the bacterium, also known as isolates 11 from domestic and 11 from international sources. Both sets of samples were resistant to at least three classes of antibiotics.

In the Salmonella study, the team sequenced a total of 50 isolates of the bacterium.

Data collected by Penn State, as well as other laboratories, as part of the studies are stored on FDA's GenomeTrakr, a distributed network that allows researchers and public health officials to conduct real-time comparisons and analyses to accelerate investigations of food-borne outbreaks and reduce illness and death caused by these diseases.