Bacteria talk to each other using N-acylhomoserine lactones (AHLs) as quorum sensing (QS) signals. This signaling allows the bacteria to control gene expression of virulence factors and biofilms once a critical density has been achieved. This phenomenon, quorum sensing, is important when an infection propagates.
Now, researchers at Linköping University in Sweden are showing how bacteria control processes in human cells the same way, affecting cell migration in a dose- and time-dependent manner. When an infection is signaled, more and more bacteria gather at the site of the attack (a wound, for example). When there is a critical mass, the bacteria start acting like multicellular organisms. They form biofilms, dense structures with powers of resistance against both antibiotics and the body’s immune defense system. At the same time, they become more aggressive and increase their mobility. All these changes are triggered when the communication molecules (short fatty acids, AHLs) bind to receptors inside the bacterial cells, triggering gene expression changes.
AHLs can migrate freely through the cell membrane, so that not just in bacterial cells but also in eukaryotic cells, cellular functional changes can be identified. In low concentrations, white blood cells can be more flexible and effective, but in high concentrations the opposite occurs, which weakens our immune defenses and opens the door for progressive infections and inflammations.
The team at Linköping University has shown how AHLs can influence their host cells. Using biochemical methods, the researchers have identified a protein designated IQGAP, which they single out as the recipient of the bacteria’s message, and something of a double agent.
“The protein can both listen in on the bacteria’s communication and change the functions in its host cells,” says Elena Vikström, Ph.D., researcher in Medical Microbiology at Linkoping University. Dr. Vikstrom is the lead author on the published paper on this work.
Their laboratory studies were carried out on human epithelial cells from the intestines, which were mixed with AHLs of the same type produced by Pseudomonas aeruginosa, a tough bacterium that causes illnesses in places like the lungs, intestines, and eyes. With the help of mass spectrometry, they have been able to see which proteins bind AHLs.
“We have proof that physical contact between bacteria and epithelial cells is not always required; the influence can happen at a distance,” indicates Dr. Vikström.
The team’s discovery can open the door to new strategies for treatment where antibiotics cannot help. One possibility is designing molecules that bind to the receptor and block the signal path for the bacteria, something like putting a stick in a lock so the key won’t go in. It’s a strategy that could work with cystic fibrosis, for example, an illness where sticky mucus made of bacterial biofilm and large amounts of white blood cells are formed in the airways.
“The human pathogen Pseudomonas aeruginosa and other bacteria communicate with each other using quorum sensing. This is important for their growth, virulence, motility, and the formation of biofilms. Furthermore, eukaryotic cells ‘listen and respond’ to QS signaling, but the exact mechanisms and receptors on mammalian cells have not been identified,” says Dr. Vikstrom. “We have previously shown that N-acylhomoserine lactones (AHLs) alter epithelial barrier functions and increase chemotaxis in human neutrophils. We show in the current work that 3O-C12-HSL modulates the migration of epithelial cells in a dose- and time-dependent manner.”
The study was published in PLoS Pathogens, in an article titled “The Pseudomonas aeruginosa N-Acylhomoserine Lactone Quorum Sensing Molecules Target IQGAP1 and Modulate Epithelial Cell Migration”.
