University of Calgary, Department of Physiology and Pharmacology, Calvin Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, Calgary, AB, Canada; Microbial Sciences, MedImmune/AstraZeneca LLC, Gaithersburg, MD, USA.
University of Calgary, Department of Physiology and Pharmacology, Calvin Phoebe & Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, Calgary, AB, Canada.
Cell Host Microbe. 2019 Apr 10;25(4):526-536.e4. doi: 10.1016/j.chom.2019.02.007. Epub 2019 Mar 28.
Bacterial biofilm infections are difficult to eradicate because of antibiotic insusceptibility and high recurrence rates. Biofilm formation by Pseudomonas aeruginosa, a leading cause of bacterial keratitis, is facilitated by the bacterial Psl exopolysaccharide and associated with heightened virulence. Using intravital microscopy, we observed that neutrophilic recruitment to corneal infections limits P. aeruginosa biofilms to the outer eye surface, preventing bacterial dissemination. Neutrophils moved to the base of forming biofilms, where they underwent neutrophil extracellular trap formation (NETosis) in response to high expression of the bacterial type-3 secretion system (T3SS). NETs formed a barrier "dead zone," confining bacteria to the external corneal environment and inhibiting bacterial dissemination into the brain. Once formed, ocular biofilms were resistant to antibiotics and neutrophil killing, advancing eye pathology. However, blocking both Psl and T3SS together with antibiotic treatment broke down the biofilm and reversed keratitis, suggesting future therapeutic strategies for this intractable infection.
细菌生物膜感染难以消除，因为抗生素耐药性和高复发率。铜绿假单胞菌（一种导致细菌性角膜炎的主要原因）通过细菌 Psl 胞外多糖的形成和与毒力增强相关的生物膜形成。使用活体显微镜，我们观察到中性粒细胞对角膜感染的募集将铜绿假单胞菌生物膜限制在眼表面，防止细菌传播。中性粒细胞移动到形成生物膜的底部，在那里它们对细菌 III 型分泌系统（T3SS）的高表达作出反应，形成中性粒细胞胞外陷阱（NETosis）。NET 形成了一个“死亡区”的屏障，将细菌局限于外眼角膜环境中，并抑制细菌向大脑传播。一旦形成，眼部生物膜对抗生素和中性粒细胞杀伤具有耐药性，从而加重眼部病理。然而，用抗生素治疗联合阻断 Psl 和 T3SS 一起破坏了生物膜并逆转了角膜炎，这为这种难治性感染提供了未来的治疗策略。
