Department of Pharmacy, School of Medicine, University of Naples 'Federico II', Via Domenico Montesano 49, 80131 Naples, Italy.
Department of Biology, University of Naples 'Federico II', Via Cinthia, 80126 Naples, Italy.
Int J Mol Sci. 2023 Feb 4;24(4):3092. doi: 10.3390/ijms24043092.
Chronic lung infections in cystic fibrosis (CF) patients are triggered by multidrug-resistant bacteria such as , , and . The CF airways are considered ideal sites for the colonization and growth of bacteria and fungi that favor the formation of mixed biofilms that are difficult to treat. The inefficacy of traditional antibiotics reinforces the need to find novel molecules able to fight these chronic infections. Antimicrobial peptides (AMPs) represent a promising alternative for their antimicrobial, anti-inflammatory, and immunomodulatory activities. We developed a more serum-stable version of the peptide WMR (WMR-4) and investigated its ability to inhibit and eradicate , , and biofilms in both in vitro and in vivo studies. Our results suggest that the peptide is able better to inhibit than to eradicate both mono and dual-species biofilms, which is further confirmed by the downregulation of some genes involved in biofilm formation or in quorum-sensing signaling. Biophysical data help to elucidate its mode of action, showing a strong interaction of WMR-4 with lipopolysaccharide (LPS) and its insertion in liposomes mimicking Gram-negative and membranes. Our results support the promising therapeutic application of AMPs in the treatment of mono- and dual-species biofilms during chronic infections in CF patients.
囊性纤维化 (CF) 患者的慢性肺部感染是由多种耐药细菌引发的，如 、 和 。CF 气道被认为是细菌和真菌定植和生长的理想场所，这些细菌和真菌有利于形成难以治疗的混合生物膜。传统抗生素的无效性加剧了寻找能够对抗这些慢性感染的新型分子的必要性。抗菌肽 (AMP) 因其具有抗菌、抗炎和免疫调节活性而成为一种很有前途的替代品。我们开发了一种更稳定的肽 WMR（WMR-4），并研究了它在体外和体内研究中抑制和清除 、 、 和 生物膜的能力。我们的结果表明，该肽能够更好地抑制而不是消除单种和双种生物膜，这进一步通过下调一些参与生物膜形成或群体感应信号的基因得到证实。生物物理数据有助于阐明其作用模式，显示 WMR-4 与脂多糖 (LPS) 具有很强的相互作用，并将其插入模拟革兰氏阴性和 膜的脂质体中。我们的结果支持 AMP 在 CF 患者慢性感染期间治疗单种和双种生物膜方面的有希望的治疗应用。
