Klebsiella pneumoniae (克雷白氏肺炎桿菌) 是世界性分布的致病菌，它的感 染可引起多樣化的臨床表現。 自 1980 年代開始，一種由單一致病菌引起的化 膿性肝膿瘍被發現與K. pneumoniae 的感染由關。 儘管這個由K. pneumoniae 引 起的肝膿瘍 (K. pneumoniae liver abscess, KLA) 在臨床上的重要性已被許多流 行病學的報告確立，目前對該菌感染肝臟的分子機轉方面的瞭解卻仍相當有限。 我們初步的研究結果發現有些 KLA 菌株對哺乳動物細胞具有明顯的毒殺能力。 比較基因體學分析結果顯示在克雷白氏肺炎桿菌的基因體中帶有兩組第六型分 泌系統的基因組，命名為 T6SS (I)與 T6SS (III)。將 T6SS (I)的重要基因剔除後的 突變菌株明顯喪失對小鼠的致病以及毒殺細胞的能力。因此我們將在本研究計畫 中運用分子生物細胞生物以及生物化學的研究方法探討 T6SS (I)參與 K. pneumoniae 毒殺細胞的分子機轉以及該分泌系統表現的調控作用。本計畫的完 成將可幫助我們釐清 T6SS (I)究竟是透過何種方式影響 K. pneumoniae 的基本生 理以及致病能力的表現。 Klebsiella pneumoniae is a worldwide spread pathogen responsible for a broad spectrum of clinical syndromes. Since 1980s, a single pathogen‐induced pyogenic liver abscess has been noticed to be predominantly mediated by the primary infection of K. pneumoniae. Despite the clinical significance of K. pneumoniae liver abscess (KLA) has been established, our knowledge regarding the molecular basis of how this bacterium causes an infection in the liver is rather restricted. A number of KLA strains exhibited cytotoxicity to mammalian cells. Based on comparative genomic analyses, two distinguishable and conserved genetic loci T6SS (I) and (III) were identified harboring genes encoding for putative T6SS core components in sequenced K. pneumoniae genomes. Mutants that had in‐frame deletion on T6SS (I) genes significantly lost virulence in mice and cytotoxicity to cells. Therefore, we aim in this project to explore the molecular basis regarding the mechanism by which K. pneumoniae T6SS (I) causes cytotoxicity and how T6SS (I) expression is regulated. Molecular, cellular, and biochemical approaches will be adapted. By the completion of this project, a picture depicting the role of T6SS (I) in K. pneumoniae physiology and virulence is expected.
