Bjarnsholt Thomas, Kirketerp-Møller Klaus, Jensen Peter Østrup, Madsen Kit G, Phipps Richard, Krogfelt Karen, Høiby Niels, Givskov Michael
Bioscience and Technology, Bldg 227 BioCentrum, Technical University of Denmark, Lyngby, Denmark.
Wound Repair Regen. 2008 Jan-Feb;16(1):2-10. doi: 10.1111/j.1524-475X.2007.00283.x.
The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.
本文提出了一个假说，旨在解释为何下肢静脉溃疡、压疮和糖尿病足溃疡会发展为慢性状态。我们认为，伤口愈合不当至少部分是由于未能有效根除感染性机会致病菌所致，这种情况类似于囊性纤维化（CF）患者中发现的慢性铜绿假单胞菌感染。我们通过荧光原位杂交分析了慢性伤口切片，发现了独特的微菌落——细菌生物膜的基本结构。此前已有几位研究人员报道，生物膜形成的另一个重要特征是对各种抗菌措施和治疗的耐受性增强。此外，囊性纤维化肺部对感染细菌的免疫反应以多形核中性粒细胞（PMN）为主，我们最近发现，铜绿假单胞菌的体外生物膜会产生一种屏蔽机制，使其免受PMN的吞噬活性影响。我们推测，生物膜中存在铜绿假单胞菌，且伴随的PMN未能将其清除，分别是抗生素治疗和先天免疫系统抗菌活性无法有效根除细菌的主要原因。
