國家衛生研究院 NHRI:Item 3990099045/10684
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    题名: The klebsiella pneumoniae gene ytfL triggers microtubule disassembly in lung epithelial cells through KATNAL1
    作者: Chua, MD;Siu, LK;Yeh, K;Guttman, JA
    贡献者: National Institute of Infectious Diseases and Vaccinology
    摘要: The Gram-negative bacterium Klebsiella pneumoniae can cause septicemia, pneumonia, liver abscesses, and meningitis resulting in mortality rates as high as 44%. Unfortunately, the sub-cellular interactions of these bacteria with host cells remain poorly understood. Because many bacterial pathogens target the host cell cytoskeleton, we examined the host cell cytoskeleton of K. pneumoniae-infected lung epithelial cells. In this study, we focused on the host microtubule network and found that microtubules were severed by the microbes, which ultimately led to the disassembly of the entire microtubule network. Because severing of microtubules in lung epithelial cells are regulated by host cell mechanisms, we hypothesized that a K. pneumoniae gene product would trigger the microtubule severing events through the activation of a host microtubule severing protein. To test this hypothesis, we screened the known disease-causing proteins of K. pneumoniae and found that expression of the capsular polysaccharide, outer membrane porins, and the type VI secretion system were not important for inducing microtubule severing. Next, we constructed and screened a library encompassing essentially all (~3000) K. pneumoniae genes to identify genes that could cause this phenotype. Using this library, we identified the gene KP ytfL that caused the microtubule severing phenotype. To further characterize this novel mechanism, we immunolocalized all known epithelial cell microtubule severing proteins in K. pneumoniae-infected cells and found that the katanin-like protein 1 (KATNAL1) localized precisely to the sites of microtubule severing. Taken together, our study shows that K. pneumoniae exploits a novel strategy to disassemble epithelial cell microtubules during its infections. The disassembly of microtubules is initiated by the expression of the bacterial gene KP ytfL, which ultimately induces the host protein KATNAL1 to sever microtubules and disrupt the microtubule network of host cells.
    日期: 2017-04
    關聯: FASBE Journal. 2017 Apr;31(1, Suppl. 1):Abstract number 741.3.
    Link to: http://www.fasebj.org/content/31/1_Supplement/741.3.abstract?sid=6ed25872-c4ef-413d-bef2-85ea18a53f7b
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0892-6638&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000405461400365
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