Study Unravels Patterns of Pseudomonas Evolution in Infections
“A long-standing lore in the cystic fibrosis field says that each patient’s infection tells a unique story, and that Pseudomonas evolves in unpredictable ways,” Jennifer Bomberger, PhD, said in a press release. Bomberger is senior author of the study and a professor at the University of Pittsburgh in Pennsylvania.
“By using tools of evolutionary biology, we showed that a complicated and unwieldy field could be simplified — these microbes follow general trends that are rooted in evolutionary biology and studying those trends can help us create more effective interventions,” Bomberger said.
The study, “Adaptation and genomic erosion in fragmented Pseudomonas aeruginosa populations in the sinuses of people with cystic fibrosis,” was published in the journal Cell Reports.
Upon infection with bacteria like P. aeruginosa, evolutionary pressures will favor those bacteria that are best able to thrive under the specific conditions found inside the human body. Ultimately, this can favor the evolution of bacteria that, because they are well-adapted to living in the body, are powerful drivers of disease.
This type of evolution is called “pathoadaptation” (“patho” means “disease” in Greek). Exactly how these processes play out are poorly understood.
Now, researchers conducted detailed analyses of Pseudomonas bacteria that were infecting six people with cystic fibrosis and chronic rhinosinusitis, which is inflammation and bacterial infection of the sinuses. Among other techniques, the team employed a technology called MiPACT-HCR (microbial identification after passive clarity technique and hybridization chain reaction), which allowed them to assess in detail where the bacteria were living within the patients’ sinus tissue.
“The sinuses are like the Wild West,” said Catherine Armbruster, PhD, a postdoctoral fellow at the university and lead author of the study.
“It is striking how little we know about Pseudomonas‘s evolution in the upper respiratory tract. There is no clear guidance on how to treat chronic sinus infections in cystic fibrosis,” Armbruster said. “Even though these sinus infections probably seed bacteria down into the lungs, it’s unclear if and how those two populations interact.”
By analyzing the bacteria’s genomes, the researchers were able to identify particular mutations associated with more strongly adapted bacteria. Results suggested that, during these infections, Pseudomonas evolution occurs in two broad stages.
In the first stage, there is strong selective pressure on the bacteria from the host. Because the human body can be an inhospitable environment, the bacteria need to adapt rapidly or they won’t be able to survive. Among other features, this stage tends to select bacteria with mutations that inactivate certain processes that normally help to repair DNA.
During the first stage, bacterial colonies tend to be large and densely populated.
Then, the second stage is characterized by smaller, more sparsely populated bacteria growths. These bacteria tend to be highly pathoadapted — they often have mutations that make them better suited toward living in a human body. But, at the same time, these bacteria exhibit signs of substantial genetic drift.
Due to genetic drift, mutations that are not necessarily helpful for survival may accumulate in a small population through random chance.
“Following an initial period of adaptive evolution in response to strong selective pressures in the host, persistent P. aeruginosa resides in small, fragmented populations that are subject to stronger effects of genetic drift,” the researchers concluded.
The results “raise the question whether clinical management of [upper respiratory tract] disease could include interventions aimed at therapeutically relieving the selective pressures in the sinuses that drive evolution toward persistence,” they added.