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Pseudomonas aeruginosa Biofilm Eradication via Nitric Oxide-Releasing Cyclodextrins.
ACS Infectious Diseases ( IF 5.3 ) Pub Date : 2020-06-08 , DOI: 10.1021/acsinfecdis.0c00246
Kaitlyn R Rouillard 1 , Matthew R Markovetz 2 , Lawrence G Bacudio 2 , David B Hill 2, 3 , Mark H Schoenfisch 1, 4, 5
Affiliation  

Pseudomonas aeruginosa is the main contributor to the morbidity and mortality of cystic fibrosis (CF) patients. Chronic respiratory infections are rarely eradicated due to protection from CF mucus and the biofilm matrix. The composition of the biofilm matrix determines its viscoelastic properties and affects antibiotic efficacy. Nitric oxide (NO) can both disrupt the physical structure of the biofilm and eradicate interior colonies. The effects of a CF-like growth environment on P. aeruginosa biofilm susceptibility to NO were investigated using parallel plate macrorheology and particle tracking microrheology. Biofilms grown in the presence of mucins and DNA contained greater concentrations of DNA in the matrix and exhibited concomitantly larger viscoelastic moduli compared to those grown in tryptic soy broth. Greater viscoelastic moduli correlated with increased tolerance to tobramycin and colistin. Remarkably, NO-releasing cyclodextrins eradicated all biofilms at the same concentration. The capacity of NO-releasing cyclodextrins to eradicate P. aeruginosa biofilms irrespective of matrix composition suggests that NO-based therapies may be superior antibiofilm treatments compared to conventional antibiotics.

中文翻译:

通过释放一氧化氮的环糊精消除铜绿假单胞菌生物膜。

铜绿假单胞菌是导致囊性纤维化(CF)患者发病率和死亡率的主要因素。由于可以防止CF粘液和生物膜基质的侵袭,很少消除慢性呼吸道感染。生物膜基质的组成决定其粘弹性质并影响抗生素功效。一氧化氮(NO)既可以破坏生物膜的物理结构,也可以根除内部菌落。CF样生长环境对铜绿假单胞菌的影响使用平行板宏观流变学和颗粒跟踪微观流变学研究了生物膜对NO的敏感性。与在胰蛋白酶大豆肉汤中生长的生物膜相比,在粘蛋白和DNA存在下生长的生物膜在基质中包含更高浓度的DNA,并表现出更大的粘弹性模量。更大的粘弹性模量与对妥布霉素和粘菌素的耐受性增加有关。值得注意的是,释放NO的环糊精以相同的浓度消除了所有生物膜。不论基质成分如何,释放NO的环糊精根除铜绿假单胞菌生物膜的能力都表明,与常规抗生素相比,基于NO的疗法可能是更好的抗生物膜治疗方法。
更新日期:2020-07-10
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