Department of Microbiology, University of Washington, Seattle, WA, United States of America.
Department of Genome Sciences, University of Washington, Seattle, WA, United States of America.
PLoS Pathog. 2019 Mar 20;15(3):e1007511. doi: 10.1371/journal.ppat.1007511. eCollection 2019 Mar.
While much is known about acute infection pathogenesis, the understanding of chronic infections has lagged. Here we sought to identify the genes and functions that mediate fitness of the pathogen Pseudomonas aeruginosa in chronic wound infections, and to better understand the selective environment in wounds. We found that clinical isolates from chronic human wounds were frequently defective in virulence functions and biofilm formation, and that many virulence and biofilm formation genes were not required for bacterial fitness in experimental mouse wounds. In contrast, genes involved in anaerobic growth, some metabolic and energy pathways, and membrane integrity were critical. Consistent with these findings, the fitness characteristics of some wound impaired-mutants could be represented by anaerobic, oxidative, and membrane-stress conditions ex vivo, and more comprehensively by high-density bacterial growth conditions, in the absence of a host. These data shed light on the bacterial functions needed in chronic wound infections, the nature of stresses applied to bacteria at chronic infection sites, and suggest therapeutic targets that might compromise wound infection pathogenesis.
虽然人们对急性感染的发病机制有了很多了解，但对慢性感染的理解却滞后了。在这里，我们试图确定介导病原菌铜绿假单胞菌在慢性伤口感染中适应性的基因和功能，并更好地了解伤口中的选择环境。我们发现，来自慢性人类伤口的临床分离株经常在毒力功能和生物膜形成方面存在缺陷，并且许多毒力和生物膜形成基因对于实验小鼠伤口中的细菌适应性并不是必需的。相比之下，与厌氧生长、一些代谢和能量途径以及膜完整性相关的基因是至关重要的。这些发现与以下结果一致：一些伤口缺陷型突变体的适应性特征可以通过体外的厌氧、氧化和膜应激条件来代表，而在没有宿主的情况下，通过高密度细菌生长条件可以更全面地代表。这些数据揭示了慢性伤口感染中需要的细菌功能、慢性感染部位施加给细菌的应激性质，并提出了可能损害伤口感染发病机制的治疗靶点。
