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. |