Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
Division of Microbiology, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
NPJ Biofilms Microbiomes. 2021 Aug 4;7(1):63. doi: 10.1038/s41522-021-00234-3.
The exopolysaccharide Psl contributes to biofilm structure and antibiotic tolerance and may play a role in the failure to eradicate Pseudomonas aeruginosa from cystic fibrosis (CF) airways. The study objective was to determine whether there were any differences in Psl in P. aeruginosa isolates that were successfully eradicated compared to those that persisted, despite inhaled tobramycin treatment, in children with CF. Initial P. aeruginosa isolates were collected from children with CF undergoing eradication treatment, grown as biofilms and labeled with 3 anti-Psl monoclonal antibodies (Cam003/Psl0096, WapR001, WapR016) before confocal microscopy visualization. When grown as biofilms, P. aeruginosa isolates from children who failed antibiotic eradication therapy, had significantly increased Psl0096 binding compared to isolates from those who cleared P. aeruginosa. This was confirmed in P. aeruginosa isolates from the SickKids Eradication Cohort as well as the Early Pseudomonas Infection Control (EPIC) trial. Increased anti-Psl antibody binding was associated with bacterial aggregation and tobramycin tolerance. The biofilm matrix represents a potential therapeutic target to improve P. aeruginosa eradication treatment.
多糖 Psl 有助于生物膜结构和抗生素耐受性形成，可能在囊性纤维化 (CF) 气道中无法根除铜绿假单胞菌中发挥作用。本研究旨在确定在接受吸入妥布霉素治疗但仍持续存在的 CF 儿童中，与成功根除的铜绿假单胞菌分离株相比，其 Psl 是否存在差异。从接受根除治疗的 CF 儿童中收集初始铜绿假单胞菌分离株，作为生物膜培养并用 3 种抗 Psl 单克隆抗体（Cam003/Psl0096、WapR001、WapR016）标记，然后进行共聚焦显微镜观察。当作为生物膜生长时，与清除铜绿假单胞菌的分离株相比，未能清除抗生素的儿童的铜绿假单胞菌分离株中 Psl0096 结合显著增加。这在 SickKids 根除队列和早期铜绿假单胞菌感染控制 (EPIC) 试验中的铜绿假单胞菌分离株中得到了证实。增加的抗 Psl 抗体结合与细菌聚集和妥布霉素耐受性有关。生物膜基质代表了改善铜绿假单胞菌根除治疗的潜在治疗靶点。
