A process for controlling intracellular bacterial infections induced by membrane injury

SCIENCE, VOLUME 304, 1515~1518, 2004

Speaker: 李璟采                                 Date: 2004/11/24 14:00~15:00

Commentator: 吳俊忠 老師                            Place:Room 601

Abstract:

The macrophages usually engulf the pathogenic bacteria by phagocytosis, and kill them by fusion of the phagosomes with lysosomes that contain the antibacterial materials. Some pathogenic bacteria inhibit phagosome-lysosome fusion to evade such defense mechanism in host cells. However, the host cells can prevent bacterial evasion by an as yet unclear mechanism. It has been reported that Syt VII, one of the isoforms of synaptotagmins, is localized on the lysosomes and regulates Ca²⁺-triggered lysosomal exocytosis and membrane repair, a process similar to the phagolysosomal fusion¹. In this study, the authors found that Syt VII was indeed required for Ca²⁺-dependent phagolysosomal fusion. First, the growth of Salmonella in the host cells was significantly increased in the Syt VII -/- cells. Second, the intracellular number of Salmonella was reduced with increasing extracellular Ca²⁺ concentration and increased in the presence of EGTA in the Syt +/+ cells, but not Syt -/- cells. They then hypothesized that the possible source of membrane injury that triggered the Syt VII-mediated phgolysosomal fusion may be the type III secretion system of the bacterium. They further demonstrated that phagolysosomal fusion was much reduced in cells infect by the type III secretion system-defective mutant of Salmonella or Yersinia. Collectively, they proposed that the membrane injury inflicted by type III secretion system may activate a Syt VII-dependent phagolysosomal fusion that leads to killing of the bacteria in the cells. This may represent a new mechanism that protects the eukaryotic cells from pathogen attack.

References:

1.     Chapmam E. R., et al. Synaptotagmin: a Ca²⁺ sensor that triggers exocytosis? Nat. Rev. Mol. Cell Biol. 3, 498-509 (2002).

2.     Martinez I. et al. Synaptotagmin VII Regulates Ca²⁺-dependent Exocytosis of Lysosomes in Fibroblasts. J. Cell Biol. 148, 1141-1149 (2000).

3.     Deepannita R., et al. A process for controlling intracellular bacterial infections induced by membrane injury. Science 304, 1515 - 1518 (2004).