Paczosa Michelle K, Mecsas Joan
Graduate Program in Immunology, MERGE-ID Track, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA.
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA
Microbiol Mol Biol Rev. 2016 Jun 15;80(3):629-61. doi: 10.1128/MMBR.00078-15. Print 2016 Sep.
Klebsiella pneumoniae causes a wide range of infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Historically, K. pneumoniae has caused serious infection primarily in immunocompromised individuals, but the recent emergence and spread of hypervirulent strains have broadened the number of people susceptible to infections to include those who are healthy and immunosufficient. Furthermore, K. pneumoniae strains have become increasingly resistant to antibiotics, rendering infection by these strains very challenging to treat. The emergence of hypervirulent and antibiotic-resistant strains has driven a number of recent studies. Work has described the worldwide spread of one drug-resistant strain and a host defense axis, interleukin-17 (IL-17), that is important for controlling infection. Four factors, capsule, lipopolysaccharide, fimbriae, and siderophores, have been well studied and are important for virulence in at least one infection model. Several other factors have been less well characterized but are also important in at least one infection model. However, there is a significant amount of heterogeneity in K. pneumoniae strains, and not every factor plays the same critical role in all virulent Klebsiella strains. Recent studies have identified additional K. pneumoniae virulence factors and led to more insights about factors important for the growth of this pathogen at a variety of tissue sites. Many of these genes encode proteins that function in metabolism and the regulation of transcription. However, much work is left to be done in characterizing these newly discovered factors, understanding how infections differ between healthy and immunocompromised patients, and identifying attractive bacterial or host targets for treating these infections.
肺炎克雷伯菌可引起多种感染,包括肺炎、尿路感染、菌血症和肝脓肿。从历史上看,肺炎克雷伯菌主要在免疫功能低下的个体中引起严重感染,但最近高毒力菌株的出现和传播扩大了易感染人群的范围,包括健康和免疫功能正常的人。此外,肺炎克雷伯菌菌株对抗生素的耐药性越来越强,使得这些菌株引起的感染治疗极具挑战性。高毒力和耐药菌株的出现推动了近期的一些研究。有研究描述了一种耐药菌株在全球的传播以及对控制感染很重要的宿主防御轴——白细胞介素-17(IL-17)。荚膜、脂多糖、菌毛和铁载体这四个因素已经得到充分研究,并且在至少一种感染模型中对毒力很重要。其他几个因素的特征描述较少,但在至少一种感染模型中也很重要。然而,肺炎克雷伯菌菌株存在大量异质性,并非每个因素在所有毒力强的克雷伯菌菌株中都发挥相同的关键作用。最近的研究已经确定了肺炎克雷伯菌的其他毒力因子,并对该病原体在各种组织部位生长的重要因素有了更多了解。这些基因中的许多编码在代谢和转录调控中起作用的蛋白质。然而,在表征这些新发现的因素、了解健康患者和免疫功能低下患者的感染差异以及确定治疗这些感染有吸引力的细菌或宿主靶点方面,仍有许多工作要做。