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RISS 인기검색어
- 검색키워드
- 저자 : Ge Ku (검색결과 4 건)
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Ku, Bonsu,Lee, Kwang-Hoon,Park, Wei Sun,Yang, Chul-Su,Ge, Jianning,Lee, Seong-Gyu,Cha, Sun-Shin,Shao, Feng,Heo, Won Do,Jung, Jae U.,Oh, Byung-Ha Public Library of Science 2012 PLoS pathogens Vol.8 No.12
<▼1><P>Upon phagocytosis, <I>Legionella pneumophila</I> translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of <I>L. pneumophila</I> belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of <I>L. pneumophila</I> and delineates the underlying molecular mechanism.</P></▼1><▼2><P><B>Author Summary</B></P><P><I>Legionella pneumophila</I> is a pathogen bacterium that causes Legionnaires' disease accompanied by severe pneumonia. Surprisingly, this pathogen invades and replicates inside macrophages, whose major function is to detect and destroy invading microorganisms. How <I>L. pneumophila</I> can be “immune” to this primary immune cell has been a focus of intensive research. Upon being engulfed by a macrophage cell, <I>L. pneumophila</I> translocates hundreds of bacterial proteins into this host cell. These proteins, called bacterial effectors, are thought to manipulate normal host cellular processes. However, which host molecules and how they are targeted by the bacterial effectors are largely unknown. In this study, we determined the three-dimensional structure of <I>L. pneumophila</I> effector protein VipD, whose function in macrophage was unknown. Ensuing analyses revealed that VipD selectively and tightly binds two host signaling proteins Rab5 and Rab22, which are key regulators of early endosomal vesicle trafficking. These interactions prevent the activated form of Rab5 and Rab22 from binding their downstream signaling proteins, resulting in the blockade of endosomal trafficking in macrophages. The presented work shows that <I>L. pneumophila</I> targets endosomal Rab proteins and delineates the underlying molecular mechanism, providing a new insight into the pathogen's strategies to dysregulate normal intracellular processes.</P></▼2>
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In vitro and in vivo photodynamic therapy of otitis media in gerbils.
Jung, Jae Yun,Kwon, Pil Seung,Ahn, Jin Chul,Ge, Ruifeng,Suh, Myung-Whan,Rhee, Chung-Ku Triological Foundation [etc.] 2009 The Laryngoscope Vol.119 No.9
<P>OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the antibacterial effects of photodynamic therapy (PDT) on common bacteria causing otitis media with effusion (OME). METHODS: An in vitro study was carried out using a hematoporphyrin derivative sensitizer (Photogem; Lemonosov Institute of Fine Chemical, Moscow, Russia) and a 632-nm diode laser on Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. The presence of colony-forming units of the bacteria was examined, the microscopic structures of the bacteria were examined by transmission electron microscopy (TEM), and flow cytometry of the bacteria was performed. An in vivo PDT study was performed using gerbils. S. pneumoniae or H. influenzae were injected into bullae. The Photogem was injected into the bullae 2 days later when OME developed, and transcanal irradiation with the 632-nm diode laser (90 J) was performed. Middle ear and bulla were washed with Dulbecco's phosphate buffered saline (DPBS) and the washed DPBS was cultured. The presence of bacterial colonies was examined. RESULTS: The PDT was effective in killing all three kinds of bacteria. TEM showed damaged bacterial cell membranes and cytoplasmic structures, and the flow cytometry showed a lower number of viable bacteria in the PDT group compared to the control group. PDT was effective in killing S. pneumoniae in 87% of the infected bullae with OME, whereas it was effective in eradicating H. influenzae in 50% of the infected bullae with OME. CONCLUSIONS: The results of these studies demonstrated that PDT may be effective to treat otitis media. PDT may have clinical implications in the treatment of otitis media that is resistant to antibiotic therapy.</P>
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