Title Morphological changes in human gastric epithelial cells induced by nuclear targeting of Helicobacter pylori urease subunit A
Author Jung Hwa Lee1, So Hyun Jun1, Jung-Min Kim2, Seung Chul Baik2*, and Je Chul Lee1*
Address 1Department of Microbiology, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea, 2Department of Microbiology, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju 660-701, Republic of Korea
Bibliography Journal of Microbiology, 53(6),406-414, 2015,
DOI 10.1007/s12275-015-5085-5
Key Words nuclear targeting protein, urease, pathogenesis, outer membrane vesicles
Abstract Nuclear targeting of bacterial proteins and their pathological effects on host cells are an emerging pathogenic mechanism in bacteria. We have previously reported that urease subunit A (UreA) of Helicobacter pylori targets the nuclei of COS-7 cells through nuclear localization signals (NLSs). This study further investigated whether UreA of H. pylori targets the nuclei of gastric epithelial cells and then induces molecular and cellular changes in the host cells. H. pylori 26695 strain produced and secreted outer membrane vesicles (OMVs). UreA was translocated into gastric epithelial AGS cells through outer membrane vesicles (OMVs) and then targeted the nuclei of AGS cells. Nuclear targeting of rUreA did not induce host cell death, but resulted in morphological changes, such as cellular elongation, in AGS cells. In contrast, AGS cells treated with rUreAΔNLS proteins did not show this morphological change. Next generation sequencing revealed that nuclear targeting of UreA differentially regulated 102 morphogenesis- related genes, of which 67 and 35 were up-regulated and down-regulated, respectively. Our results suggest that nuclear targeting of H. pylori UreA induces both molecular and cellular changes in gastric epithelial cells.