Jones Bradley D, Faron Matthew, Rasmussen Jed A, Fletcher Joshua R
Department of Microbiology, The University of Iowa Carver College of Medicine Iowa City, IA, USA ; The Genetics Program, The University of Iowa Carver College of Medicine Iowa City, IA, USA ; The Midwest Regional Center for Excellence in Biodefense and Emerging Infectious Disease Research, Washington University St. Louis, MO, USA.
The Genetics Program, The University of Iowa Carver College of Medicine Iowa City, IA, USA.
Front Cell Infect Microbiol. 2014 Mar 7;4:32. doi: 10.3389/fcimb.2014.00032. eCollection 2014.
Over the last decade, studies on the virulence of the highly pathogenic intracellular bacterial pathogen Francisella tularensis have increased dramatically. The organism produces an inert LPS, a capsule, escapes the phagosome to grow in the cytosol (FPI genes mediate phagosomal escape) of a variety of host cell types that include epithelial, endothelial, dendritic, macrophage, and neutrophil. This review focuses on the work that has identified and characterized individual virulence factors of this organism and we hope to highlight how these factors collectively function to produce the pathogenic strategy of this pathogen. In addition, several recent studies have been published characterizing F. tularensis mutants that induce host immune responses not observed in wild type F. tularensis strains that can induce protection against challenge with virulent F. tularensis. As more detailed studies with attenuated strains are performed, it will be possible to see how host models develop acquired immunity to Francisella. Collectively, detailed insights into the mechanisms of virulence of this pathogen are emerging that will allow the design of anti-infective strategies.
在过去十年中,关于高致病性细胞内细菌病原体土拉弗朗西斯菌毒力的研究急剧增加。该生物体产生惰性脂多糖、荚膜,能逃离吞噬体在包括上皮细胞、内皮细胞、树突状细胞、巨噬细胞和中性粒细胞在内的多种宿主细胞类型的胞质溶胶中生长(FPI基因介导吞噬体逃逸)。本综述聚焦于已鉴定和表征该生物体单个毒力因子的研究工作,我们希望强调这些因子如何共同发挥作用以产生该病原体的致病策略。此外,最近发表了几项研究,对土拉弗朗西斯菌突变体进行了表征,这些突变体可诱导野生型土拉弗朗西斯菌菌株中未观察到的宿主免疫反应,而野生型菌株可诱导针对强毒株攻击的保护作用。随着对减毒株进行更详细的研究,将有可能了解宿主模型如何对弗朗西斯菌产生获得性免疫。总体而言,对该病原体毒力机制的详细见解正在浮现,这将有助于设计抗感染策略。