The nosocomial pathogen Pseudomonas aeruginosa colonizes the lung mucosa (blue) by forming two distinct subpopulations – sessile (red) and motile (green) bacteria. Credit: Benoit-Joseph Laventie, Biozentrum, University of Basel
Key points:
- Pseudomonas aeruginosa forms two subpopulations to improve colonization success
- Division is controlled by a genetic switch that affects c-di-GMP levels
- Identification of this division mechanism can aid in treatment strategies
Researchers have revealed that the antibiotic-resistant bacterium Pseudomonas aeruginosa, a common cause of hospital-acquired pneumonia, splits into two subpopulations to successfully colonize the body. The discovery of the genetic mechanism behind this dual strategy can aid in more effective treatment strategies.
A team from the University of Basel found that P. aeruginosa populations split into sessile and motile groups to maximize colonization success. While the sessile group attaches to mucosal surfaces and forms a robust biofilm, the motile group spreads out into other surrounding tissues.
This “division of labor,” also known as the “stick and run” mechanism, improves the chance that a fraction of the population will survive under different stress conditions, explained first author Christina Manner. While motile bacteria disperse to infect other areas of the body, sessile bacteria in biofilms are protected from immune cells.
For the study, published in Nature Microbiology, the researchers performed genetic analyses to uncover how this split occurs. They discovered that a stochastic genetic switch regulates levels of the signaling molecule c-di-GMP in the bacteria.
Bacteria with a high c-di-GMP concentration will stick to surfaces and form a biofilm, while lower c-di-GMP levels lead to motile bacteria that spread to other areas. This revelation could lead to better treatments that target the switching mechanism.
“We now better understand how Pseudomonas aeruginosa manages to spread and thrive on lung mucosa,” said project leader Urs Jenal. “By identifying the genetic switch, we have tracked down the Achilles heel of the pathogen.”
The researchers further demonstrated that Disperazol, a recently-discovered anti-biofilm compound, already targets the switching mechanism to increase the proportion of motile bacteria, said Jenal. This study shows the potential for similar compounds to disrupt the surface colonization strategy of P. aeruginosa.