Bacteria make some common moves when setting up house in the lungs of people with cystic fibrosis, a new study finds.
A new study of
Pseudomonas aeruginosa
bacteria isolated from cystic fibrosis patients with chronic lung infections shows that the microbe may evolve similarly in everyone who contracts it, researchers reported online September 21 in
mBio
. Consistent changes in the activity of 24 genes may provide the bacteria with a competitive advantage when infecting the lungs — and an Achilles’ heel that scientists might exploit.
“If some of these selective changes are key to the survival of the organism, then those are natural targets for therapy,” says George O’Toole, a microbiologist at Dartmouth Medical School in Hanover, N.H.
Researchers led by Marvin Whiteley, a microbial geneticist and physiologist at the University of Texas at Austin, examined gene activity profiles of
P. aeruginosa
bacteria isolated over the course of eight years from three cystic fibrosis patients with chronic lung infections. People with cystic fibrosis, a genetic disease that leads to the buildup of thick mucus in the lungs, often contract
P. aeruginosa
infections that last decades. The bacteria form structured colonies known as biofilms that are virtually impervious to antibiotics.
Whiteley’s group and others have previously mapped genetic changes that the bacteria undergo during long-term infections. But knowing where mutations are in the microbe’s genes doesn’t tell scientists anything about how those alterations affect an organism’s behavior.
Whiteley’s group took a “quite innovative” approach to learn more about how bacteria evolve in the human lung, O’Toole says. Instead of mapping DNA mutations, the researchers tracked changes in gene activity over the course of the patients’ infections. “By using [gene activity] profiling you’re able to look at changes that are likely to have bigger functional implications for the organism,” he says.
Before embarking on the study, other scientists thought they knew what Whiteley would find in people with long-term lung infections: bacteria that produce excess mucus. Such slimy bacteria are notoriously hard to kill and make likely candidates for long-term infections. “Most people were expecting us to say that all the strains were mucoid, but we found that’s only a proportion of strains,” Whiteley says.
Another prediction was that each patient’s set of bacteria would follow a separate evolutionary path, responding to unique conditions within each individual such as oxygen concentrations, availability of nutrients, pressure from the immune system and antibiotics. The researchers did find hundreds of genes that followed different evolutionary paths among the three patients, but a core group of 24 genes changed in parallel in all three people.
Most of the genes have no known function, but a few give clues to what
Pseudomonas
must do to survive and thrive in the lungs. For instance, all three of the strains shut down genes that make fimbriae, hairlike structures on the surface of the cell that help the bacteria adhere to surfaces. The immune system often uses fimbrial proteins as homing devices to direct attacks against the bacteria, so losing the hairs may help
Pseudomonas
evade detection by the immune system, Whiteley says.
In order to prove that the changes are adaptive, the researchers would need to test such hypotheses by directly assessing how each change in gene activity affects the evolutionary fitness of the organism in the lungs, O’Toole says. “To me it’s amazing that we found anything at all,” Whiteley says. His group is now trying to determine whether all people who get chronic
Pseudomonas
infections have bacteria that evolve along the parallel lines identified in this study. The results could be important in designing new drugs to combat the stubborn infections.
“When you’re looking for new targets for therapeutics you want something that is the same in everyone,” he says.
