Effect of ubiquitin-proteasome system and autophagy-lysosome pathway on intracellular replication of Brucella.suis

Abstract

The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) are two major protein degradation pathways in eukaryotic cells. In the present study, we investigated the role of two systems and their interaction after Brucella.suis (B.suis) infected RAW264.7 murine macrophage. We demonstrated that B.suis activated ALP by upregulating LC3-Ⅱlevels as well as incomplete inhibition of P62 expression in RAW264.7 cells. On the other hand, we used pharmacological agents to confirm that ALP contributed the intracellular proliferation of B.suis. At present, the studies on the relationship between UPS and Brucella remain less understanding. In the study, we demonstrated that UPS machinery was also activated by promoting expression of 20 s proteasome after B.suis infected RAW264.7 cells, and that, the UPS could also promote intracellular proliferation of B.suis. Many recent studies propose the close link and dynamic interconversion between UPS and ALP. Currently, the experiments demonstrated that after RAW264.7 cells infected B.suis, ALP was activated following UPS inhibition, while the UPS was not effectively activated after ALP inhibition. Last, we compared the ability to promote intracellular proliferation of B.suis between UPS and ALP. The results displayed that the ability of UPS to promote intracellular proliferation of B.suis was stronger than that of ALP, and simultaneous inhibition of UPS and ALP led to seriously affection on intracellular proliferation of B.suis. All above, our research provides a better understanding on the interaction between Brucella and both systems.

Keywords: Autophagy-lysosome pathway; Brucella; Interaction; Proliferation; Ubiquitin-proteasome system.