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

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 rUreA?NLS 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.

Cross‐Reactivity of Polyclonal Antibodies against Canavalia ensiformis (Jack Bean) Urease and Helicobacter pylori Urease Subunit A Fragments

“…Recent reports have revealed that UreA also plays an important and multi‐faceted role for bacteria. There is growing recognition that sub‐unit A contributes to stabilizing the shape of the whole enzyme molecule, and can modulate the activity of urease on a pathway that is not as yet fully understood . It has even been reported that a monoclonal antibody (termed S3) is capable of recognizing the conformational structure of UreA of H .…”

“…This suggests that UreA of H . pylori may have an influence on morphological changes in human gastric epithelial cells …”

Role of Probiotics in Managing of Helicobacter Pylori Infection: A Review

“…The pathogenic role inside the gastroduodenal tract was first described by Marshall and Warren. All infectious strains of H. pylori produce and secrete large quantities of the urease enzyme that allows for colonization of the gastric epithelium, and consequently, neutralizing the acidic environment of the gastric lumen [4,5]. Gastric colonization with H. pylori results stomach chronic gastritis which in most cases will be subclinical.…”

“…Moreover, probiotics could modulate the host immunologic response via interacting with the epithelial cells, and consequently alter the release of anti-inflammatory effectors, which would leads in a reduction of gastric inflammation [5]. However, the effect of probiotics on the immune response is difficult to simplify, because certain probiotics strains may produce diverse immune responses, which depend on the host's immune status [4].…”

Tracking the cargo of extracellular symbionts into host tissues with correlated electron microscopy and nanoscale secondary ion mass spectrometry imaging

“…Promising candidates include proteins in the OMVs. A study of 49 Helicobacter pylori proteins with a nuclear localization signal showed that almost half did traffic to the nucleus (Lee, Jun, Kim, Baik, & Lee, 2015). The V. fischeri OMV proteome has over 200 proteins (Lynch et al, 2019), and three of the proteins have a nuclear localization signal in all of the 13 symbiotic V. fischeri strains that have a full-genome sequence.…”