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Helicobacter pylori outer inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitro
Authors:Anis Rageh Al‐Maleki  Mun Fai Loke  Sook Yin Lui  Nur Siti Khadijah Ramli  Yalda Khosravi  Chow Goon Ng  Gopinath Venkatraman  Khean‐Lee Goh  Bow Ho  Jamuna Vadivelu
Institution:1. Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;2. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;3. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;4. Singapore Precision Medicine Centre Pte Ltd, Singapore, Singapore
Abstract:Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA “on” and “off” motifs. Proteomics analysis was performed on AGS cell pre‐infection and postinfection with Hpylori oipA “on” and “off” strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down‐regulated postinfection with oipA “off” strains comparing to oipA “on” strains. Furthermore, oipA “off” and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell‐cycle arrest than oipA “on” strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of Hpylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA “on” strains predominates.
Keywords:H     pylori  infection  LC/Q‐TOF MS  oipA  proteomic
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