https://scholars.lib.ntu.edu.tw/handle/123456789/190836
標題: | Klebsiella pneumoniae Translocates across the Intestinal Epithelium via Rho GTPase- and Phosphatidylinositol 3-Kinase/Akt-Dependent Cell Invasion | 作者: | Hsu, Chun-Ru Pan, Yi-Jiun Liu, Ju-Yun Chen, Chun-Tang Lin, Tzu-Lung Wang, Jin-Town McCormick, B. A. |
公開日期: | 2015 | 起(迄)頁: | 769-779 | 來源出版物: | Infection and Immunity | 摘要: | Klebsiella pneumoniae is an important pathogen that causes hospital-acquired septicemia and is associated with the recent emergence of community-acquired pyogenic liver abscess (PLA). Clinical typing suggests that K. pneumoniae infections originate from the gastrointestinal reservoir. However, the underlying mechanism remains unknown. Here, we have sought to determine how K. pneumoniae penetrates the intestinal barrier. We identified that bacteremia and PLA clinical isolates adhered to and invaded intestinal epithelial cells. Internalization of K. pneumoniae in three different human colonic cell lines was visualized by confocal microscopy and three-dimensional (3D) imaging. Using a Transwell system, we demonstrated that these K. pneumoniae isolates translocated across a polarized Caco-2 monolayer. No disruptions of transepithelial electrical resistance and altered distribution of tight junction protein ZO-1 or occludin were observed. Therefore, K. pneumoniae appeared to penetrate the intestinal epithelium via a transcellular pathway. Using specific inhibitors, we characterized the host signaling pathways involved. Inhibition by cytochalasin D and nocodazole suggested that actin and microtubule cytoskeleton were both important for K. pneumoniae invasion. A Rho inhibitor, ML141, LY294002, and an Akt1/2 inhibitor diminished K. pneumoniae invasion in a dose-dependent manner, indicating that Rho family GTPases and phosphatidylinositol 3-kinase (PI3K)/Akt signaling were required. By a mouse model of gastrointestinal colonization, in vivo invasion of K. pneumoniae into colonic epithelial cells was demonstrated. Our results present evidence to describe a possible mechanism of gastrointestinal translocation for K. pneumoniae. Cell invasion by manipulating host machinery provides a pathway for gut-colonized K. pneumoniae cells to penetrate the intestinal barrier and access extraintestinal locations to cause disease. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/270659 | DOI: | 10.1128/IAI.02345-14 | SDG/關鍵字: | cytochalasin D; nocodazole; occludin; phosphatidylinositol 3 kinase; protein kinase B; protein ZO1; Rho guanine nucleotide binding protein; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; chromone derivative; cytochalasin D; morpholine derivative; nocodazole; nucleic acid synthesis inhibitor; occludin; Ocln protein, mouse; phosphatidylinositol 3 kinase; protein kinase B; protein ZO1; Rho guanine nucleotide binding protein; Tjp1 protein, mouse; tubulin modulator; Article; bacteremia; bacterium isolate; CACO 2 cell line; cell invasion; colon; confocal microscopy; controlled study; cytoskeleton; electric resistance; epithelium cell; filters and membranes; host; human; human cell; human cell culture; image analysis; in vivo study; inhibition kinetics; internalization; intestine cell; intestine epithelium; intestine epithelium cell; Klebsiella pneumoniae; microtubule; mouse model; nonhuman; polarization; priority journal; pyogenic liver abscess; signal transduction; three dimensional imaging; transcellular fluid; actin filament; animal; antagonists and inhibitors; Bagg albino mouse; female; immunology; intestine mucosa; Klebsiella infection; Klebsiella pneumoniae; metabolism; microbiology; mouse; pathogenicity; physiology; tight junction; tumor cell line; Actin Cytoskeleton; Animals; Bacteremia; Caco-2 Cells; Cell Line, Tumor; Chromones; Cytochalasin D; Female; Humans; Intestinal Mucosa; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred BALB C; Microtubules; Morpholines; Nocodazole; Nucleic Acid Synthesis Inhibitors; Occludin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; rho GTP-Binding Proteins; Signal Transduction; Tight Junctions; Tubulin Modulators; Zonula Occludens-1 Protein |
顯示於: | 醫學系 |
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