Treatment of Pseudomonas aeruginosa Biofilm Present in Endotracheal Tubes by Poly-L-Lysine

Abstract

The endotracheal tube (ETT) is an essential interface between the patient and ventilator in mechanically ventilated patients. However, a microbial biofilm is formed gradually on this tube and is associated with the development of ventilator-associated pneumonia. The bacteria present in the biofilm are more resistant to antibiotics, and current medical practices do not make it possible to eliminate. Pseudomonas aeruginosa is one of the leading pathogens that cause biofilm infections and ventilator-associated pneumonia. Poly-L-lysine (pLK) is a cationic polypeptide possessing antibacterial properties and mucolytic activity by compacting DNA. Here, we explored the antibiofilm activity of pLK to treat P. aeruginosa biofilms on ETTs while taking into consideration the necessary constraints for clinical translation in our experimental designs. First, we showed that pLK eradicates a P. aeruginosa biofilm formed in vitro on 96-well microplates. We further demonstrated that pLK alters bacterial membrane integrity, as revealed by scanning electron microscopy, and eventually eradicates biofilm formed either by reference or clinical strains of P. aeruginosa biofilms generated in vitro on ETTs. Second, we collected the ETT from patients with P. aeruginosa ventilator-associated pneumonia. We observed that a single dose of pLK is able to immediately disrupt the biofilm structure and kills more than 90% of bacteria present in the biofilm. Additionally, we did not observe any lung tolerance issue when the pLK solution was instilled into the ETT of ventilated pigs, an animal model particularly relevant to mimic invasive mechanical ventilation in humans. In conclusion, pLK appears as an innovative antibiofilm molecule, which could be applied in the ETT of mechanically ventilated patients.