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Published in CenterView on November 19, 2012
From left, Dr. Jonathan Thomas, postdoctoral researcher, Xiao Luo, laboratory researcher, and Dr. Ashley Robinson, associate professor of microbiology
From left, Dr. Jonathan Thomas, postdoctoral researcher, Xiao Luo, laboratory researcher, and Dr. Ashley Robinson, associate professor of microbiology

Robinson uses next-gen technology to unravel bacteria’s mutations

By Jack Mazurak

The explosive pace of technology is giving scientists insight into how tiny disease-causing bacteria mutate and spread on local, nationwide and worldwide scales.

Dr. Ashley Robinson, associate professor of microbiology, uses genetics to track changes in methicillin-resistant Staphylococcus aureus, or MRSA, and to understand its spread over time.

“Microorganisms don’t have feathers where you can easily tell them apart,” he said. “You have to look at their genes to tell one strain from another.”

Propelled by next-generation DNA sequencing machines, faster computers and logarithmically larger databases, researchers like Robinson can now process and analyze exponentially more information than just a couple of years ago.

In a study published in June by Proceedings of the National Academy of Sciences, Robinson and his coauthors used information from 87 MRSA genomes to map its spread throughout the United Kingdom. For the study, Robinson collaborated with researchers at the University of Edinburgh, the University of Cambridge, the Broad Institute of the Massachusetts Institute of Technology and Harvard University, the University of Bath and other health-service and governmental institutions.

Like detectives, the researchers pieced together gene mutations in the 87 samples to trace the bacteria’s emergence, adaptation and transmission. They found particular strains had spread from hospitals in large population centers like London and Glasgow, to smaller regional ones.

Dr. Rathel “Skip” Nolan, professor and director of infectious diseases, treats cases of MRSA, works to control its spread and is also involved in research.

“Basically, what Ashley’s group has uncovered is that there are certain strains of MRSA that get around and into people more easily,” Nolan said. “And that’s fascinating. It’s a very basic question that they’ve answered and additional research will tell us more.

“Ultimately you would hope that this work would lead to better ways of containing and preventing the spread of MRSA.”

The Journal of the American Medical Association reported decreases of 28 percent in life-threatening infections of hospital-acquired MRSA from 2005 through 2008, and 17 percent in community-acquired infections. Still, MRSA remains a deadly problem.

The U.S. Centers for Disease Control and Prevention explains on its website that understanding the burden of MRSA – how much is occurring, where it is happening and how it is being spread – is essential for developing effective prevention programs and measuring their impact.

Technology will help scientists answer those questions. In the past 20 years, technology radically changed the field of bacterial population genetics, which only emerged in the 1980s.

Before DNA sequencing became commonplace in the 1990s, scientists could only indirectly compare snippets of genes, which made strain comparisons dicey. The field moved more heavily into DNA sequencing in the early 2000s.

“We went from targeted-sequence sampling of a genome to sequencing an entire genome,” Robinson said.

Recently the cost of next-generation DNA sequencers has dropped and their speed has increased. Researchers can now sequence multiple whole genomes in 24 hours.

“Just a couple of years ago, scientists published a paper using eight MRSA genomes,” said Robinson, in comparison to the 87 genomes sequenced in the June 5 PNAS article. “(This technology) is what we in bacterial population genetics have been waiting for. Before, it had been a very theory-rich, data-poor field of study. But now, we have the technology to sequence multiple strains.”

Robinson, his postdoc, Dr. Jonathan Thomas, and lab technician Xiao Luo have moved on to a bigger project. They plan to map 300-400 MRSA genomes using a next-generation DNA sequencer the Medical Center installed in September.

Nolan said MRSA has been a problem for decades in hospitals but wasn’t seen to a great extent in outside communities. In the late 1990s, a very toxic strain – USA300 – emerged in the community and spread.

“That’s what Ashley and his group are trying to unravel: How this occurred and what were the genetic mutations this particular strain and other strains underwent,” Nolan said.

Decoding genomes of hundreds of USA300 samples will help Robinson and his colleagues construct a bacterial family history.

“There’s probably an elaborate family tree underlying USA300,” Robinson said. “We want to look at more than 300 isolates to unravel, or at least peek, at the underlying genotypes.”

They’ll also compare its evolution to another strain, USA100, common in hospitals for a half-century.

“That aspect of the study will let us see if there are adaptive variations between the two groups,” he said.

Robinson recently reapplied for a grant through the National Institute of General Medical Sciences to fund the study.