the coxiella burnetii doticm system delivers a unique repertoire of type iv effectors into host cells and is required for intracellular replication伯纳特氏立克次氏体的doticm系统提供了一个独特的iv型效应器需要进入宿主细胞和细胞内复制.pdfVIP

The Coxiella burnetii Dot/Icm System Delivers a Unique Repertoire of Type IV Effectors into Host Cells and Is Required for Intracellular Replication 1. 1. ¨ 1,2 1 Kimberly L. Carey , Hayley J. Newton , Anja Luhrmann , Craig R. Roy * 1 Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America, 2 Microbiology Institute, University Clinic Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Germany Abstract Coxiella burnetii, the causative agent of human Q fever, is an intracellular pathogen that replicates in an acidified vacuole derived from the host lysosomal network. This pathogen encodes a Dot/Icm type IV secretion system that delivers bacterial proteins called effectors to the host cytosol. To identify new effector proteins, the functionally analogous Legionella pneumophila Dot/Icm system was used in a genetic screen to identify fragments of C. burnetii genomic DNA that when fused to an adenylate cyclase reporter were capable of directing Dot/Icm-dependent translocation of the fusion protein into mammalian host cells. This screen identified Dot/Icm effectors that were proteins unique to C. burnetii, having no overall sequence homology with L. pneumophila Dot/Icm effectors. A comparison of C. burnetii genome sequences from different isolates revealed diversity in the size and distribution of the genes encoding many of these effectors. Studies examining the localization and function of effectors in eukaryotic cells provided evidence that several of these proteins have an affinity for specific host organelles and can disrupt cellular functions. The identification of a transposon insertion mutation that disrupts the dot/icm locus was used to validat