Walker Travis S, Tomlin Kerry L, Worthen G Scott, Poch Katie R, Lieber Jonathan G, Saavedra Milene T, Fessler Michael B, Malcolm Kenneth C, Vasil Michael L, Nick Jerry A
National Jewish Medical and Research Center, D202, 1400 Jackson Street, Denver, CO 80206, USA.
Infect Immun. 2005 Jun;73(6):3693-701. doi: 10.1128/IAI.73.6.3693-3701.2005.
Cystic fibrosis (CF) lung disease features persistent neutrophil accumulation to the airways from the time of infancy. CF children are frequently exposed to Pseudomonas aeruginosa, and by adulthood, 80% of CF patients are chronically infected. The formation of biofilms is a particularly important phenotypic characteristic of P. aeruginosa that allows for bacterial survival despite aggressive antibiotic therapy and an exuberant immune response. Here, we show that the presence of neutrophils enhances initial P. aeruginosa biofilm development over a period of 72 h through the formation of polymers comprised of actin and DNA. F-actin was found to be a site of attachment for P. aeruginosa. These actin and DNA polymers are present in CF sputum, and disruption of the polymers dispersed the associated P. aeruginosa cells and reduced biofilm development. These findings demonstrate a potential maladaptation of the primary innate response. When the host fails to eradicate the infection, cellular components from necrotic neutrophils can serve as a biological matrix to facilitate P. aeruginosa biofilm formation.
囊性纤维化(CF)肺部疾病的特征是从婴儿期开始中性粒细胞持续在气道中积聚。CF患儿经常接触铜绿假单胞菌,到成年时,80%的CF患者会受到慢性感染。生物膜的形成是铜绿假单胞菌一个特别重要的表型特征,使得细菌在积极的抗生素治疗和旺盛的免疫反应下仍能存活。在此,我们表明中性粒细胞的存在通过由肌动蛋白和DNA组成的聚合物的形成,在72小时内增强了铜绿假单胞菌生物膜的初始发育。发现F-肌动蛋白是铜绿假单胞菌的附着位点。这些肌动蛋白和DNA聚合物存在于CF痰液中,聚合物的破坏使相关的铜绿假单胞菌细胞分散,并减少了生物膜的发育。这些发现证明了主要先天反应的潜在适应不良。当宿主无法根除感染时,坏死中性粒细胞的细胞成分可作为生物基质促进铜绿假单胞菌生物膜的形成。