鑑定克雷伯氏菌引發的‘嗜中性球胞外捕捉’及肝膿瘍的分子機制
Identification of the molecular mechanism of Klebsiella pneumoniae NTUH K2044-induced NETs formation and liver abscess
克雷伯氏肺炎桿菌是造成社區性感染重要的致病菌，可造成肺炎及肝膿瘍。遭遇細菌感染時，嗜中性球會利用吞噬作用或是胞外捕捉生成來結合並殺死胞外細菌。本研究發現克雷伯氏菌NTUH-K2044於體外可誘發嗜中性球胞外捕捉生成。分析NTUH-K2044菌株的全基因體帶有負責編譯第六型分泌系統的基因，可能參與宿主與致病原間的交互作用。剔除NTUH-K2044菌株第六型分泌系統的作用蛋白質和它的結構蛋白質基因，皆顯著地降低對嗜中性球胞外捕捉生成的活性。克雷伯氏菌肝膿瘍菌株可利用此系統在小鼠體內競爭造成感染。NTUH-K2044第六型分泌系統的基因剔除菌株在小鼠敗血症感染模式中皆顯著有致病力減弱的情形。由本研究獲得的結果將有助於我們了解克雷伯氏菌第六型分泌系統的致病機制，可能藉此找到有潛力之治療標的。
Klebsiella pneumoniae is an important pathogen causing community-acquired infections such as pneumonia and community-acquired pyogenic liver abscess (PLA). When encountered bacterial infection, neutrophils could engulf and kill the bacteria either by phagocytosis or form neutrophil extracellular traps (NETs) to bind and kill pathogens extracellularly. In this study, the K. pneumoniae NTUH-K2044 strain could induce NETs formation in vitro. Analysis of the genome of NTUH-K2044 strain revealed this strain harbors putative type VI secretion system (T6SS)-encoding genes which likely account for the host and pathogen interaction. Deletion of T6SS effector and structural proteins-encoding genes of the NTUH-K2044 all significantly reduced the activity of NETs formation. The PLA-associated K. pneumoniae utilized the T6SS-mediated competition to establish infection in mice. The NTUH-K2044 strain deleted for the T6SS genetic loci was profoundly attenuated in virulence as demonstrated in the mouse model of septicemia. These results obtained from this study will help us to understand the pathogenic mechanism of T6SS in K. pneumoniae and might identify potential targets for therapeutic design.
