Department of Microbiology and Medical Science, Chungnam National University School of Medicine, 266 Munwha-ro, Jung-gu, Daejeon 35015, Republic of Korea.
Pathog Dis. 2017 Nov 30;75(8). doi: 10.1093/femspd/ftx107.
Autophagy is known to be a vital homeostatic defense process that controls mycobacterial infection. However, the relationship between autophagy response and the virulence of Mycobacterium abscessus strain UC22 has not been reported. Here, we demonstrate that M. abscessus induces autophagy and inhibits autophagy flux in murine macrophages. Further, the rough variant of M. abscessus, UC22 that is a highly virulent clinical isolate, significantly inhibited autophagic flux than the smooth variant of M. abscessus ATCC 19977. In addition, it was noticed that the intracellular survival of UC22 is significantly enhanced by blocking the autophagosome-lysosome fusion in macrophages compared to the smooth variant. However, Mycobacterium smegmatis did not block autophagy flux in murine macrophages. Besides, we confirmed that the lipid components of M. abscessus UC22 play a role in autophagosome formation. These data suggest that the virulent M. abscessus might be able to survive and grow within autophagosomes by preventing the autophagosome-lysosome fusion and their clearance from the cells.
自噬被认为是一种重要的体内平衡防御过程，可控制分枝杆菌感染。然而，自噬反应与脓肿分枝杆菌 UC22 菌株毒力之间的关系尚未报道。在这里，我们证明了脓肿分枝杆菌诱导了鼠巨噬细胞中的自噬，并抑制了自噬流。此外，粗糙型脓肿分枝杆菌 UC22 是一种高致病性的临床分离株，其自噬流的抑制作用明显强于光滑型脓肿分枝杆菌 ATCC19977。此外，与光滑型相比，在巨噬细胞中阻断自噬体-溶酶体融合后，UC22 的细胞内存活显著增强。然而，耻垢分枝杆菌不会阻断鼠巨噬细胞中的自噬流。此外，我们证实了脓肿分枝杆菌 UC22 的脂质成分在自噬体形成中发挥作用。这些数据表明，毒力较强的脓肿分枝杆菌可能能够通过阻止自噬体-溶酶体融合及其从细胞中清除来在自噬体中存活和生长。
