Morphological changes in human gastric epithelial cells induced by nuclear targeting of Helicobacter pylori urease subunit A

Jung Hwa Lee; So Hyun Jun; Jung-Min Kim; Seung Chul Baik; Je Chul Lee

doi:10.1007/s12275-015-5085-5

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Morphological changes in human gastric epithelial cells induced by nuclear targeting of Helicobacter pylori urease subunit A: Jung Hwa Lee ¹, So Hyun Jun ¹, Jung-Min Kim ², Seung Chul Baik ², Je Chul Lee ¹; Journal of Microbiology 2015;53(6):406-414.
DOI: https://doi.org/10.1007/s12275-015-5085-5
Published online: May 30, 2015

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 Korea¹Department 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

Corresponding author: Seung Chul Baik , Tel: +82-53-420-4844,
Je Chul Lee , Tel: +82-53-420-4844,

Received: 12 February 2015 • Revised: 14 May 2015 • Accepted: 15 May 2015

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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.

Keywords: nuclear targeting protein;urease;pathogenesis;outer membrane vesicles

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Morphological changes in human gastric epithelial cells induced by nuclear targeting of Helicobacter pylori urease subunit A

J. Microbiol. 2015;53(6):406-414. Published online May 30, 2015

DOI: https://doi.org/10.1007/s12275-015-5085-5

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