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The role of Psl in the failure to eradicate Pseudomonas aeruginosa biofilms in children with cystic fibrosis
npj Biofilms and Microbiomes ( IF 7.8 ) Pub Date : 2021-08-04 , DOI: 10.1038/s41522-021-00234-3
Amanda J Morris 1 , Lindsay Jackson 1 , Yvonne Cw Yau 2 , Courtney Reichhardt 3 , Trevor Beaudoin 1 , Stephanie Uwumarenogie 1 , Kevin M Guttman 1 , P Lynne Howell 4, 5 , Matthew R Parsek 3 , Lucas R Hoffman 6 , Dao Nguyen 7 , Antonio DiGiandomenico 8 , David S Guttman 9 , Daniel J Wozniak 10 , Valerie J Waters 1, 11, 12
Affiliation  

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.



中文翻译:

Psl 在未能根除囊性纤维化儿童铜绿假单胞菌生物膜中的作用

胞外多糖 Psl 有助于生物膜结构和抗生素耐受性,并且可能在未能从囊性纤维化 (CF) 气道中根除铜绿假单胞菌方面发挥作用。该研究的目的是确定在CF 儿童中,尽管吸入妥布霉素治疗,但与那些持续存在的铜绿假单胞菌分离株相比,Psl 是否存在任何差异。最初的铜绿假单胞菌分离株是从接受根除治疗的 CF 儿童身上收集的,生长为生物膜,并在共聚焦显微镜可视化之前用 3 种抗 Psl 单克隆抗体(Cam003/Psl0096、WapR001、WapR016)标记。当作为生物膜生长时,铜绿假单胞菌与清除铜绿假单胞菌的分离物相比,抗生素根除治疗失败的儿童分离物的 Psl0096 结合显着增加。这在来自 SickKids Eradication Cohort 以及早期假单胞菌感染控制 (EPIC) 试验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目标。

更新日期:2021-08-04
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