"Imagine if you could interrogate the bacteria," said Kishony, principal investigator on the study. "You would ask, 'what do you find most challenging in the human body?'"
In search of a good model system, Kishony and his graduate student Jean-Baptiste Michel consulted clinicians and found their way to Alex McAdam, an associate professor of pathology at Children's Hospital Boston who suggested B. dolosa. "I thought it would be interesting," McAdam said, "because we could also see how the organism changed during the course of an outbreak."
From that conversation grew a robust collaboration among a diverse team of scientists and clinicians, including Kishony's lab, McAdam and Greg Priebe, assistant professor of anesthesia at Children's and a microbiologist at the Channing Laboratory of Brigham and Women's Hospital, as well as collaborators in Michigan and Virginia. The team set out to sequence the genomes of 112 B. dolosa isolates taken from 14 of the infected patients, mapping genetic changes over time to reveal both the route of the infection's spread and which genes faced the greatest selective pressure in other words, how the bacteria evolved when challenged by human defenses and medical treatment.
Every time a cell divides, small copying errors can introduce slight changes in the new DNA. Some of those changes affect the cell's machinery, and some do not. To identify selective pressure on genes over generations, scientists compare the number of significant changes to the number of those that had no effecta measure called the dN/dS ratio.
"That's where we ran into a bit of a snag," said Michel, now a postdoctoral fellow at Harvard University and visiting faculty at Google, who analyzed the data with Tami Lieberman when both were graduate students in Syste
|Contact: David Cameron|
Harvard Medical School