Portelinha Jasmin, Angeles-Boza Alfredo M
Department of Chemistry, University of Connecticut, 55 N. Eagleville Road Storrs, Connecticut, CT 06269, USA.
Institute of Material Science, University of Connecticut, 97 N. Eagleville Road Storrs, Connecticut, CT 06269, USA.
Chembiochem. 2021 May 4;22(9):1646-1655. doi: 10.1002/cbic.202000816. Epub 2021 Feb 24.
Bacterial infections in cystic fibrosis (CF) patients are an emerging health issue and lead to a premature death. CF is a hereditary disease that creates a thick mucus in the lungs that is prone to bacterial biofilm formation, specifically Pseudomonas aeruginosa biofilms. These biofilms are very difficult to treat because many of them have antibiotic resistance that is worsened by the presence of extracellular DNA (eDNA). eDNA helps to stabilize biofilms and can bind antimicrobial compounds to lessen their effects. The metallo-antimicrobial peptide Gaduscidin-1 (Gad-1) eradicates established P. aeruginosa biofilms through a combination of modes of action that includes nuclease activity that can cleave eDNA in biofilms. In addition, Gad-1 exhibits synergistic activity when used with the antibiotics kanamycin and ciprofloxacin, thus making Gad-1 a new lead compound for the potential treatment of bacterial biofilms in CF patients.
囊性纤维化(CF)患者的细菌感染是一个新出现的健康问题,并会导致过早死亡。CF是一种遗传性疾病,会在肺部产生浓稠的黏液,易于形成细菌生物膜,特别是铜绿假单胞菌生物膜。这些生物膜很难治疗,因为其中许多具有抗生素抗性,而细胞外DNA(eDNA)的存在会使这种抗性恶化。eDNA有助于稳定生物膜,并能结合抗菌化合物以减轻其作用。金属抗菌肽加杜西丁-1(Gad-1)通过多种作用方式根除已形成的铜绿假单胞菌生物膜,这些作用方式包括可切割生物膜中eDNA的核酸酶活性。此外,Gad-1与抗生素卡那霉素和环丙沙星联合使用时表现出协同活性,因此使Gad-1成为潜在治疗CF患者细菌生物膜的一种新的先导化合物。