Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Cell Microbiol. 2019 Mar;21(3):e12977. doi: 10.1111/cmi.12977. Epub 2018 Nov 22.
Klebsiella pneumoniae raises significant concerns to the health care industry as these microbes are the source of widespread contamination of medical equipment, cause pneumonia as well as other multiorgan metastatic infections and have gained multidrug resistance. Despite soaring mortality rates, the host cell alterations occurring during these infections remain poorly understood. Here, we show that during in vitro and in vivo K. pneumoniae infections of lung epithelia, microtubules are severed and then eliminated. This destruction does not require direct association of K. pneumoniae with the host cells, as microtubules are disassembled in cells that are distant from the infecting bacteria. This microtubule dismantling is dependent on the K. pneumoniae (Kp) gene ytfL as non-pathogenic Escherichia coli expressing Kp ytfL disassemble microtubules in the absence of K. pneumoniae itself. Our data points to the host katanin catalytic subunit A like 1 protein (KATNAL1) and the katanin regulatory subunit B1 protein (KATNB1) as the gatekeepers to the microtubule severing event as both proteins localise specifically to microtubule cut sites. Infected cells that had either of these proteins knocked out maintained intact microtubules. Taken together, we have identified a novel mechanism that a bacterial pathogen has exploited to cause microtubule destruction within the host epithelia.
肺炎克雷伯菌对医疗保健行业构成了重大威胁，因为这些微生物是医疗设备广泛污染的源头，可导致肺炎以及其他多器官转移性感染，并已获得多种药物耐药性。尽管死亡率飙升，但宿主细胞在这些感染过程中发生的变化仍知之甚少。在这里，我们表明，在体外和体内肺炎克雷伯菌感染肺上皮细胞的过程中，微管被切断，然后被消除。这种破坏不需要肺炎克雷伯菌与宿主细胞的直接关联，因为微管在远离感染细菌的细胞中被拆卸。这种微管拆卸依赖于肺炎克雷伯菌（Kp）基因 ytfL，因为表达 Kp ytfL 的非致病性大肠杆菌在没有肺炎克雷伯菌本身的情况下就会拆卸微管。我们的数据指向宿主 katanin 催化亚基 A 样 1 蛋白（KATNAL1）和 katanin 调节亚基 B1 蛋白（KATNB1）作为微管切割事件的守门员，因为这两种蛋白都特异性地定位于微管切割部位。敲除了这两种蛋白中的任何一种的感染细胞都保持着完整的微管。总之，我们已经确定了一种新的机制，即细菌病原体利用这种机制在宿主上皮细胞内引起微管破坏。
