Targeting Bacteria Cell Wall Elements Can Fight Chronic P. aeruginosa Infection, Study Suggests

Targeting Bacteria Cell Wall Elements Can Fight Chronic P. aeruginosa Infection, Study Suggests

Targeting some elements in the bacterial cell wall can be an effective way to activate the immune system and fight chronic, treatment-resistant Pseudomonas aeruginosa infections, according to a study.

The finding was reported in a study titled “Profiling the susceptibility of Pseudomonas aeruginosa strains from acute and chronic infections to cell-wall-targeting immune proteins,” published in the journal Nature Scientific Reports.

Many patients with chronic respiratory diseases, including cystic fibrosis (CF), have an increased risk of developing severe lung infections triggered by P. aeruginosa. This can contribute to lung function worsening and poorer outcomes.

Throughout the years, many antibacterial agents have been developed to help fight such life-threatening infections. However, common bacteria strains have begun to become resistant to these therapies. Fighting treatment-resistant bacterial infections has become a major concern in the medical community.

Human immune cells naturally produce proteins to target important bacteria cell wall elements, called peptidoglycans (PGNs). With this strategy, the immune system can block some of the natural protective mechanisms of bacteria.

Spanish researchers have now evaluated the antibacterial potential of these immune-produced proteins — namely lysozyme and PGN Recognition Proteins (PGLYRPs) — to fight treatment-resistant infections.

The team used P. aeruginosa strains collected from two infection scenarios: acute infections, with bacteria isolated from the bloodstream; and chronic infections, with bacteria collected from the lungs of CF patients. They exposed the different bacteria strains to immune-produced lysozyme or PGLYRPs.

Overall, results showed that the antibacterial activity of these proteins alone was modest for the majority of the strains.

Treatment with lysozyme promoted the death of about 40-50% of the bacteria, while PGLYRPs showed even lower activity, with mean bacterial survival rates around 80%. No significant differences were observed between strains collected from CF patients and blood samples.

Interestingly, when the team used either lysozyme or PGLYRPs in combination with a permeabilizer compound (subinhibitory colistin — a compound that disrupts the permeability of the bacterial cell wall), the antibacterial activity was enhanced. CF-related strains in particular were found to be more susceptible than blood bacteria strains, with about a threefold decrease in survival.

“The reason some strains showed outstanding viability decreases for some of the combined treatments still remains to be ascertained,” researchers said. “However, an obvious explanation could be the colistin susceptibility of each strain.”

The increased bacterial susceptibility to the combo treatment could result from particular changes in PNGs and their metabolism. On the other hand, niche adaptation in the case of CF could also contribute to bacteria cell-wall protein changes, and consequent responsiveness to treatment.

“Therefore, each strain’s [presentation] should be individually approached to ascertain the molecular basis, with it being very difficult to draw general trends,” the researchers said.

Still, the study’s findings suggest that using subinhibitory colistin as permeabilizer, or by targeting cell wall elements, may help increase the body’s immune activity against P. aeruginosa.

According to the team, the results suggest “that attacking some P. aeruginosa cell-wall biology-related elements to increase the activity of our innate weapons could be a promising therapeutic strategy.”

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