Molecular Immunology, Helmholtz Center for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany.
Microbes Infect. 2012 Sep;14(11):951-8. doi: 10.1016/j.micinf.2012.04.002. Epub 2012 Apr 13.
The ability of opportunistic bacterial pathogens to grow in biofilms is decisive in the pathogenesis of chronic infectious diseases. Growth within biofilms does not only protect the bacteria against the host immune system but also from the killing by antimicrobial agents. Here, we introduce a mouse model in which intravenously administered planktonic Pseudomonas aeruginosa bacteria are enriched in transplantable subcutaneous mouse tumors. Electron microscopy images provide evidence that such bacteria reside in the tumor tissue within biofilm structures. Immunohistology furthermore demonstrated that infection of the tumor tissue elicits a host response characterized by strong neutrophilic influx. Interestingly, the biofilm defective PA14 pqsA transposon mutant formed less biofilm in vivo and was more susceptible to clearance by intravenous ciprofloxacin treatment as compared to the wild-type control. In conclusion, we have established an experimentally tractable model that may serve to identify novel bacterial and host factors important for in vivo biofilm formation and to re-evaluate bactericidal and anti-biofilm effects of currently used and novel antibacterial compounds.
机会性病原体细菌在生物膜中生长的能力对慢性传染病的发病机制起决定性作用。在生物膜内生长不仅可以保护细菌免受宿主免疫系统的攻击，还可以免受抗菌药物的杀伤。在这里，我们引入了一种小鼠模型，其中静脉内给予的浮游态铜绿假单胞菌在可移植的皮下小鼠肿瘤中富集。电子显微镜图像提供了证据，表明这些细菌存在于生物膜结构内的肿瘤组织中。免疫组织化学进一步表明，肿瘤组织的感染引发了以强烈中性粒细胞浸润为特征的宿主反应。有趣的是，与野生型对照相比，生物膜缺陷型 PA14 pqsA 转座子突变体在体内形成的生物膜较少，并且更容易被静脉内环丙沙星治疗清除。总之，我们建立了一种具有实验可行性的模型，可用于鉴定体内生物膜形成的重要细菌和宿主因子，并重新评估目前使用的和新型抗菌化合物的杀菌和抗生物膜作用。
