Departement of Microbiology, Kyungpook National University School of Medicine, Daegu, South Korea.
FEMS Microbiol Lett. 2012 Jun;331(1):17-24. doi: 10.1111/j.1574-6968.2012.02549.x. Epub 2012 Apr 13.
Outer membrane vesicles (OMVs) derived from pathogenic Gram-negative bacteria are an important vehicle for delivery of effector molecules to host cells, but the production of OMVs from Klebsiella pneumoniae, an opportunistic pathogen of both nosocomial and community-acquired infections, and their role in bacterial pathogenesis have not yet been determined. In the present study, we examined the production of OMVs from K. pneumoniae and determined the induction of the innate immune response against K. pneumoniae OMVs. Klebsiella pneumoniae ATCC 13883 produced and secreted OMVs during in vitro culture. Proteomic analysis revealed that 159 different proteins were associated with K. pneumoniae OMVs. Klebsiella pneumoniae OMVs did not inhibit cell growth or induce cell death. However, these vesicles induced expression of proinflammatory cytokine genes such as interleukin (IL)-1β and IL-8 in epithelial cells. An intratracheal challenge of K. pneumoniae OMVs in neutropenic mice resulted in severe lung pathology similar to K. pneumoniae infection. In conclusion, K. pneumoniae produces OMVs like other pathogenic Gram-negative bacteria and K. pneumoniae OMVs are a molecular complex that induces the innate immune response.
外膜囊泡(OMVs)来源于致病性革兰氏阴性菌,是向宿主细胞输送效应分子的重要载体,但来自机会性病原体肺炎克雷伯菌(医院和社区获得性感染的病原体)的 OMVs 的产生及其在细菌发病机制中的作用尚未确定。在本研究中,我们研究了肺炎克雷伯菌 OMVs 的产生,并确定了针对肺炎克雷伯菌 OMVs 的先天免疫反应的诱导。肺炎克雷伯菌 ATCC 13883 在体外培养过程中产生和分泌 OMVs。蛋白质组学分析表明,有 159 种不同的蛋白质与肺炎克雷伯菌 OMVs 相关。肺炎克雷伯菌 OMVs 不会抑制细胞生长或诱导细胞死亡。然而,这些囊泡诱导上皮细胞中促炎细胞因子基因(如白细胞介素(IL)-1β和 IL-8)的表达。在中性粒细胞减少症小鼠的气管内挑战肺炎克雷伯菌 OMVs 导致类似于肺炎克雷伯菌感染的严重肺部病理。总之,肺炎克雷伯菌像其他致病性革兰氏阴性菌一样产生 OMVs,肺炎克雷伯菌 OMVs 是诱导先天免疫反应的分子复合物。