New research provides insights into how bacteria “talk” to each other in lung infections, which could provide strategies to block these signals and ease bacterial virulence in patients with cystic fibrosis (CF).
The study, “Spatial determinants of quorum signaling in a Pseudomonas aeruginosa infection model,” was published in the journal Proceedings of the National Academy of Sciences.
Quorum sensing is a process through which bacteria send and receive molecules to regulate gene levels in response to changes in cell density. The process may lead to altered virulence or the ability to establish an infection. But little is known about quorum sensing or bacterial growth during infection.
“Much of what is known about quorum sensing comes from studies of large populations of bacteria in an environment that does not compare with the natural infection site,” Sophie Darch, PhD, the study’s lead author, said in a Georgia Tech news story by A. Maureen Rouhi.
Darch said that in infections, bacteria are often found in small, dense clusters, which are called aggregates.
To address this process, researchers created an environment similar to a chronic lung infection in cystic fibrosis. One of the most prevalent infectious agents in the lung of CF patients is the bacteria Pseudomonas aeruginosa, which is resistant to many antibiotics and represents a frustrating clinical problem in immuno-compromised patients.
Investigators at Georgia Institute of Technology (Georgia Tech) used a synthetic CF sputum media (SCFM2), which recreates the makeup of lung secretions from cystic fibrosis patients. Aggregates of P. aeruginosa in SCFM2 are similar to those found in CF patients.
The team collaborated with researchers at the University of Texas at Austin to determine how close bacteria need to be to each other for effective communication between then.
Bacterial aggregates in infection “vary in size and can be separated by large distances,” said Georgia Tech Prof. Marvin Whiteley, the study’s senior author.
For this purpose, the scientists developed a micro-3D printing platform to better mimic the distribution of bacterial aggregates in infections.
In their experiments, they enclosed a producer cell in a tiny trap, which is filled after multiple cell divisions. SCFM2-containing aggregates of responder cells are then laid over this trap.
Results revealed a one-way communication of signals from producer to responder aggregates, which was verified by the change from the color red to green in responders.
Scientists observed that bacterial aggregates containing about 2,000 cells, which are a little larger than those in CF lungs, could not signal to other aggregates.
For bacterial communication to take place, aggregates had to contain at least 5,000 cells, which is about five times the size of aggregates in CF lungs, Darch said.
“From these data, communication is likely confined within an individual aggregate rather than being a population-wide phenomenon,” she said.
Researchers previously thought that bacterial communication could take place over large distances. But in cystic fibrosis lungs, bacterial aggregates are scattered and separated by large distances, which makes them unlikely to “talk” to each other.
“This study identifies a critical role for spatial distribution and bacterial phenotypic heterogeneity in bacterial signaling during infection,” the investigators wrote.
As for the implications in cystic fibrosis, Darch said that “understanding better how bacteria communicate has the potential to find ways of disrupting the communication and potentially diminishing bacterial virulence.”
“The study provides benchmark data for how quorum sensing might proceed in an environment similar to the CF lung,” Whiteley added. He said that in other diseases in which bacterial aggregates have different sizes, communication may be different.
Whiteley emphasized that additional work is needed to deepen the understanding of spatial requirements for bacterial communication in CF and other infections.