burkholderia cenocepacia type vi secretion system mediates escape of type ii secreted proteins into the cytoplasm of infected macrophages伯克cenocepacia vi型分泌系统调节ii型分泌蛋白质释放到细胞质被感染的巨噬细胞.pdf

Burkholderia cenocepacia Type VI Secretion System Mediates Escape of Type II Secreted Proteins into the Cytoplasm of Infected Macrophages 1,2 1 1 3 1 Roberto Rosales-Reyes , Daniel F. Aubert , Jennifer S. Tolman , Amal O. Amer , Miguel A. Valvano * 1 Centre for Human Immunology, Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada, 2 Laboratorio de ´ ´ ´ ´ ´ ´ Infectologıa, Microbiologıa e Inmunologıa Clınicas, Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico ´ City, Mexico, 3 Centre for Microbial Interface Biology, Department of Microbial Infection and Immunity and the Department of Internal Medicine, Ohio State University, Columbus, Ohio, United States of America Abstract Burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. We have previously shown that bacterial survival occurs in bacteria- containing membrane vacuoles (BcCVs) resembling arrested autophagosomes. Intracellular bacteria stimulate IL-1b secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion system (T6SS) is required for these phenotypes but surprisingly it is not required for the maturation arrest of the BcCV. Here, we show that macrophages infected with B. cenocepacia employ