[ODP-120] 宿主の遺伝子発現を調整する野兎病菌エフェクターIglCの解析
Francisella tularensis is the causative agent of tularemia. The type VI secretion system encoded by Francisella Pathogenic Island (FPI) is known to be essential for the intracellular growth of F. tularensis. However, its function has not been fully elucidated. In this study, we focused on the FPI gene iglC, and analyzed its function.F. tularensis sub. novicida (F. novicida) lacking iglC showed decreased intracellular growth in human monocyte cell line THP-1 cells. Expression of IglC in HeLa cells showed that IglC was present in the cytoplasm or nucleus. Expression of IglC also showed cytotoxicity to the cells. Immunoprecipitation assay demonstrated that IglC was co-precipitated with heat shock cognate 71 kDa protein (Hsc70). Pull-down assay revealed that IglC bound to the C-terminal domain of Hsc70, but not to its substrate-binding domain. Hsc70 is translocated into the nucleus by heat shock at 40°C, and IglC expressed in HeLa cells was translocated into the nucleus with Hsc70 by heat shock. As the results of RNA-Seq analysis of HeLa cells expressing IglC, the expression of several genes was altered. These results indicate that IglC is essential for the intracellular growth of F. novicida, and suggest that IglC may be translocated into the host nucleus by binding to Hsc70 and contribute to intracellular growth by affecting the gene expression of host cells in some way.