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Nuclear targeting of bacterial proteins has emerged as a pathogenic mechanism whereby bacterial proteins induce host cell pathology. In this study, we examined nuclear targeting of  Acinetobacter baumannii  transposase (Tnp) and subsequent epigenetic changes in host cells. Tnp of  A. baumannii  ATCC 17978 possesses nuclear localization signals (NLSs),  225 RKRKRK 230 . Transient expression of  A. baumannii  Tnp fused with green fluorescent protein (GFP) resulted in the nuclear localization of these proteins in COS-7 cells, whereas the truncated Tnp without NLSs fused with GFP were exclusively localized in the cytoplasm.  A. baumannii  Tnp was found in outer membrane vesicles, which delivered this protein to the nucleus of host cells. Nuclear expression of  A. baumannii  Tnp fused with GFP in A549 cells induced DNA methylation of CpG regions in the promoters of  E-cadherin  ( CDH1 ) gene, whereas the cytoplasmic localization of the truncated Tnp without NLSs fused with GFP did not induce DNA methylation. DNA methylation in the promoters of  E-cadherin  gene induced by nuclear targeting of  A. baumannii  Tnp resulted in down-regulation of gene expression. In conclusion, our data show that nuclear traffic of  A. baumannii  Tnp induces DNA methylation of CpG regions in the promoters of  E-cadherin  gene, which subsequently down-regulates gene expression. This study provides a new insight into the epigenetic control of host genes by bacterial proteins.

Nuclear Translocation of Acinetobacter baumannii Transposase Induces DNA Methylation of CpG Regions in the Promoters of E-cadherin Gene