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. Bacteria present in the biofilm are more resistant to antibiotics and current medical practices do not make it possible to eliminate. P. 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. We explored here the anti-biofilm activity of pLK to treat P. aeruginosa biofilms on ETT, taking into consideration the necessary constraints for clinical translation in our experimental designs. First, we showed that pLK eradicate 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 eradicate biofilm formed either by reference or clinical strains of P. aeruginosa biofilms generated in vitro on ETT. Second, we collected 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 biofilm. Additionally, we did not observe any lung tolerance issue when pLK solution was instilled into ETT of ventilated-pigs, an animal model particularly relevant to mimic invasive mechanical ventilation in humans. In conclusion, pLK appears as an innovative anti-biofilm molecule which could be applied in the ETT of mechanically-ventilated patients.
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