INSERM, Centre d'Etude des Pathologies Respiratoires, U1100, Tours, France.
University of Tours, France.
Antimicrob Agents Chemother. 2018 Oct 24;62(11). doi: 10.1128/AAC.00564-18. Print 2018 Nov.
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. 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 biofilms on ETTs while taking into consideration the necessary constraints for clinical translation in our experimental designs. First, we showed that pLK eradicates a biofilm formed 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 biofilms generated on ETTs. Second, we collected the ETT from patients with 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.
气管内导管（ETT）是机械通气患者中患者与呼吸机之间的重要接口。然而，这个管上会逐渐形成微生物生物膜，并且与呼吸机相关性肺炎的发生有关。生物膜中的细菌对抗生素的耐药性更强，而目前的医疗实践并不能将其消除。铜绿假单胞菌是导致生物膜感染和呼吸机相关性肺炎的主要病原体之一。聚赖氨酸（pLK）是一种阳离子多肽，具有抗菌特性和通过压缩 DNA 具有黏液溶解活性。在这里，我们探索了 pLK 的抗生物膜活性，以治疗 ETT 上的铜绿假单胞菌生物膜，同时在我们的实验设计中考虑到临床转化的必要限制。首先，我们表明 pLK 可以消除在 96 孔微孔板上形成的铜绿假单胞菌生物膜。我们进一步表明，pLK 改变了细菌膜的完整性，如扫描电子显微镜所揭示的，最终消除了参考或临床菌株的生物膜形成的生物膜，以及在 ETT 上生成的生物膜。其次，我们从患有呼吸机相关性肺炎的患者中收集了 ETT。我们观察到，单次剂量的 pLK 能够立即破坏生物膜结构，并杀死生物膜中存在的超过 90%的细菌。此外，当将 pLK 溶液注入通气猪的 ETT 中时，我们没有观察到任何肺部耐受问题，通气猪是一种特别相关的动物模型，可以模拟人类的侵入性机械通气。总之，pLK 似乎是一种创新的抗生物膜分子，可应用于机械通气患者的 ETT。
