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Published on: June 29, 2017
Klebsiella pneumoniae disassembles host microtubules in lung epithelial cells
Michael Dominic Chua1, Ci-Hong Liou2, Alexander Constantine Bogdan1
1Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Abstract:
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.
Insights
Klebsiella pneumoniae infection severs and eliminates host cell microtubules, even in distant cells. This process is mediated by the K. pneumoniae ytfL gene and host proteins KATNAL1 and KATNB1.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Background:
- Klebsiella pneumoniae is a multidrug-resistant pathogen causing severe infections.
- The host cell alterations during K. pneumoniae infections are not well understood.
- Microtubules play crucial roles in cellular structure and function.
Purpose of the Study:
- To investigate the impact of K. pneumoniae infection on host cell microtubules.
- To identify the bacterial and host factors involved in microtubule disruption.
Main Methods:
- In vitro and in vivo infection models using K. pneumoniae and lung epithelia.
- Genetic manipulation of K. pneumoniae (ytfL gene) and host cells (KATNAL1, KATNB1).
- Microscopy and protein localization studies.
Main Results:
- K. pneumoniae infection leads to microtubule severing and elimination in host lung epithelia.
- Microtubule destruction occurs even in cells not directly infected by bacteria.
- The K. pneumoniae ytfL gene is essential for microtubule dismantling.
- Host proteins KATNAL1 and KATNB1 are identified as key mediators of microtubule severing.
Conclusions:
- K. pneumoniae employs a novel mechanism to disrupt host cell microtubules.
- The bacterial ytfL gene and host katanin proteins are critical for this process.
- Understanding this mechanism may offer new therapeutic targets against K. pneumoniae infections.
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