Title Page
Abstract
General introduction
Contents
List of abbreviations 19
Chapter 1. External cell wall lipid in Mycobacteroides abscessus induces ferroptosis and dissemination 21
Introduction 22
Materials and methods 25
Results 33
Discussion 53
Chapter 2. Pyruvate dehydrogenase kinase inhibitor Dichloroacetate augments autophagy mediated constraining the replication of Mycobacteroides massiliense in macrophages 56
Introduction 57
Materials and methods 60
Results 67
Discussion 85
Reference 89
국문초록 96
Chapter 1 17
Figure 1. Characterization of M. abscessus smooth (MaSm) and rough (MaRg) variant isolates.[이미지참조] 40
Figure 2. MaRg triggers ferroptosis in BMDMs by a mechanism associated with increased intracellular iron, lipid peroxidation, and...[이미지참조] 41
Figure 3. MaRg infection regulates iron export transporters.[이미지참조] 43
Figure 4. MaRg external cell wall lipid induces iron accumulation via TLR2-dependent signaling.[이미지참조] 44
Figure 5. PIMs from MaRg extracellular cell wall lipid regulate iron export transporters.[이미지참조] 46
Figure 6. PIMs from MaRg induces iron accumulation via TLR2-dependent signaling.[이미지참조] 48
Figure 7. Accumulated iron in MaRg-infected macrophages drive mitochondrial ROS production.[이미지참조] 49
Figure 8. MaRg induces ferroptosis to promote MaRg pathogenicity and dissemination in vivo.[이미지참조] 51
Chapter 2 18
Figure 1. DCA decreased glycolysis and intracellular M. massiliense in macrophages. 73
Figure 2. DCA alone had no effect on macrophage viability, bacterial growth. 75
Figure 3. AMPKa1 deficiency impairs glycolytic and OXPHOS activity in macrophages. 76
Figure 4. DCA increased phosphorylated AMPKα1 in M. massiliense-infected macrophages. 78
Figure 5. DCA-induced autophagy enhances clearance of intracellular M. massiliense in macrophages. 80
Figure 6. DCA increased the colocalization of phagosomes and lysosomes against M. massiliense infection. 82
Figure 7. Schematic depiction of DCA-induced autophagy on M. massiliense infection. 84