WIKIMEDIA, LHOONStaphylococcus bacteria from people’s noses produce amino acids that curb secretions of antimicrobial proteins in the sinus, according to a report published yesterday (September 5) in Science Signaling. The amino acids activate sweet taste receptors present on sinus cells, suggesting that pharmaceutical inhibition of these receptors may have the potential to treat sinus infections.
“This work expands upon a direction of research involving taste receptors and identifies mechanisms by which Staphylococcus bacteria modulate host immunity via interactions with these receptors,” says Martin Desrosiers of the University of Montreal who was not involved with the project. “It also helps explain how bacteria can contribute to the development and persistence of chronic rhinosinusitis,” he adds.
Taste receptors are only called taste receptors because they were first discovered on tongue cells, explains Robert Lee of the University of Pennsylvania Perelman School of Medicine in Philadelphia. But in fact, he says, “they are just chemosensors,” and are found in many different parts of the body, such as the kidney, pancreas, brain, and sinus. “We only know the tip of the iceberg of what they are doing” in these various locations, adds Lee, who for his part is focusing on the functions of those found up the human nose.
It’s known that bacterial molecules can activate bitter taste receptors in the human sinus and that, in turn, this promotes the secretion of antimicrobial proteins. It’s also known that the activation of sweet taste receptors on the same cells suppresses this bitter receptor response, thus suppressing antimicrobial protein secretion.
One theory of how these two phenomenon interact is that glucose, present in small amounts in nasal secretions, would stop sinus cells from killing commensal bacteria in times of normal health, but that overgrowth of pathogenic bacteria might diminish glucose levels (because the bugs eat it). The drop in sugar levels would then relieve the suppression of the bitter receptor response and increase antimicrobial secretions.
Another possibility is that bacteria-produced sweet compounds, such as D-amino acids (amino acid isomers that do not create proteins, but instead function as components of cell walls, signaling molecules, and more), could suppress the antimicrobial secretions, enabling the microbes to colonize. Although the two ideas are not mutually exclusive, Lee and colleagues’ new results provide evidence of this latter scenario.
First, the team examined whether nasal bacteria do in fact produce sweet D-amino acids. They took nasal swabs from volunteers, cultured the bacteria, and found that in cultures where Staphylococcus bacteria predominated, the sweet amino acids D-Leu and D-Phe were produced, while in cultures where Pseudomonas aeruginosa predominated, they were not. Overgrowth of either species can cause sinusitis.
The next question was, “How do these molecules affect the host?” says Lee. To find out, the team grew human sinus cells in culture, treated them with denatonium (a compound that stimulates the bitter receptor and induces antimicrobial protein secretion), and then added D-Leu or D-Phe. Both amino acids could prevent the denatonium-induced antimicrobial production, and could also enhance the ability of Staphylococcus bacteria to infect the sinus cells. Inhibiting the sweet receptor prevented these effects of D-Leu and D-Phe.
Clinical trials of bitter taste receptor activators to boost antimicrobial protein production in chronic sinusitis patients are currently underway, says Lee. But, based on these new results, it’s possible that sweet receptor inhibitors may work just as well, especially in patients where Staphylococcus bacteria are causing the infection. Encouragingly, the sweet receptor inhibitor used in this study is a safe and commercially available compound called lactisole, used in jellies and jams to cut down the sweetness and enhance fruit flavors, Lee explains.
“Overall, this is probably one of the most exciting things we have going on in chronic sinusitis research,” says Alex Chiu of the University of Kansas Medical Center who was not involved with the project. Current treatments for sinusitis include antibiotics and anti-inflammatories, but there are problems, Chiu says. Sometimes there is antibiotic resistance, other times the treatments simply don’t work, or the infections quickly recur. Instead of focusing on the symptoms, he says, this new line of work is aimed at “trying to find the mechanisms [behind the infections], which can then direct the therapies.”
R.J. Lee et al., “Bacterial D-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells,” Science Signaling, 10:eaam7703, 2017.