A群鏈球菌是重要的人類致病菌，可導致人類大範圍的感染，其中所造成最為嚴重的疾病為壞死性筋膜炎，能迅速的造成肌肉損壞並具有高致死性。肌肉細胞富含粒線體以提共大量能量以維持肌肉正常功能。粒線體為高度動態的雙層膜胞器，參與持續細胞能量，​​代謝和細胞凋亡。自噬作用是細胞內高度保守的細胞代謝途徑，能將受損細胞器或蛋白質進行降解。最近的研究表明粒線體參與在真核細胞中的先天免疫系統之中，幫助對抗病原體。先前的研究已報導A群鏈球菌的感染能誘導宿主內自噬作用發生，也被定義為異源吞噬，然而A群鏈球菌的胞內清除機制是細胞類型依賴性的。在我們的初步結果中，A群鏈球菌感染可以誘導肌肉細胞自噬。本研究，我們再次證明在壞死性筋膜炎患者的肌肉組織中的肌肉破壞伴隨著LC3斑點的增加，表明GAS感染引起與自噬相關的人體肌肉破壞。有趣的是，使用自噬抑製劑，3-MA和巴弗洛黴素A1，胞內細菌數量則減少，說明肌肉細胞自噬可能對肌細胞內細菌存活力提供保護作用。此外，我們還發現A群鏈球菌感染後會造成肌肉細胞粒線體的受損和損失。進一步檢查粒線體損失是否由粒線體自噬介導，發現自噬標記LC3-II積累在肌肉細胞的粒線體上。此外，我們通過MT-mKeima red檢測了GAS誘導的線粒體自噬，並觀察到586 nm處的紅色螢光信號增加，表明GAS感染通過完整的線粒體流程誘導線粒體自噬。然而在A群鏈球菌感染後，粒線體自噬分子PINK1和Parkin並未轉移到粒線體上，並發現是由BNIP3 / NIX介導的粒線體自噬參與A群鏈球菌感染。利用粒線體自噬抑製劑MitoTEMPO不能降低胞內細菌的存活，然而MitoQ能降低胞內細菌的存活率。BNIP3 / NIX的敲低也抑制了A群鏈球菌感染後的胞內細菌存活。我們的研究證明A群鏈球菌感染中粒線體數量的控制，能對於細菌發病機制中粒線體的功能提供新的見解。

Group A Streptococcus (GAS) is an important human pathogen and cause a broad range of human diseases, including necrotizing fasciitis (NF), a severe disease of sudden onset that rapidly muscle destruction with high lethality. Muscles are responsible for energetic functions requiring a large amount of energy which is mostly provided by mitochondria. Mitochondria are dynamic double-membrane-bound organelles that involved in cellular energy, metabolism and apoptosis. Moreover, recent studies had demonstrated that mitochondria participate in innate immune system against intracellular pathogen. Autophagy is a highly conserved cellular metabolic pathway by degradation of intracellular damaged organelles or proteins, and is also an anti-bacterial defense system in eukaryotic cells. GAS has been reported to induce autophagy, also defined as xenophagy, however, the following consequence of bacterial clearance appears to be cell-type-dependent. Our previous results demonstrated GAS induced muscular autophagy. Here, we first confirmed this GAS-induced muscular destruction associated with increased of LC3 puncta in human muscle tissue from patient with necrotizing fasciitis. Interestingly, intracellular bacterial numbers were decreased by treatment with autophagy inhibitors, indicating that this autophagy might provide a protective effect for intracellular survival in muscle cells. In addition, we also found muscular mitochondria was damaged and loss after GAS infection. To further linkage of these observations, we examined whether the mitochondrial loss is mediated by mitophagy, we isolated the muscular mitochondria and found autophagic marker, LC3-II, was accumulated. Further, we examined the GAS-induced mitophagy by MT-mKeima red and observed an increased red fluorescent signals, indicating GAS infection induced mitophagy through the completed mitophagic flux. However, two mitophagy makers, PINK1 and Parkin, were not translocated onto mitochondria after GAS infection, but BNIP3 and NIX were. Using mitophagy inhibitor, MitoTEMPO, intracellular bacterial survival was not decreased whereas intracellular bacterial survival was decreased after the blockage of mitophagy using MitoQ. Moreover, knockdown of BNIP3/NIX suppressed intracellular bacterial survival after GAS infection. Taken together, we demonstrated that the mitochondrial quantity control in GAS infection might offer insights into mitochondria function in bacterial pathogenesis.

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