title: The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression.
abstract: Bacterial infections typically elicit a strong Heat Shock Response (HSR) in host cells. However, the gastric pathogen Helicobacter pylori has the unique ability to repress this response, the mechanism of which has yet to be elucidated. This study sought to characterize the underlying mechanisms by which H. pylori down-modulates host HSP expression upon infection. Examination of isogenic mutant strains of H. pylori defective in components of the type IV secretion system (T4SS), identified the secretion substrate, CagA, to be essential for down-modulation of the HSPs HSPH1 (HSP105), HSPA1A (HSP72), and HSPD1 (HSP60) upon infection of the AGS gastric adenocarcinoma cell line. Ectopic expression of CagA by transient transfection was insufficient to repress HSP expression in AGS or HEK293T cells, suggesting that additional H. pylori factors are required for HSP repression. RT-qPCR analysis of HSP gene expression in AGS cells infected with wild-type H. pylori or isogenic cagA-deletion mutant found no significant change to account for reduced HSP levels. In summary, this study identified CagA to be an essential bacterial factor for H. pylori-mediated suppression of host HSP expression. The novel finding that HSPH1 is down-modulated by H. pylori further highlights the unique ability of H. pylori to repress the HSR within host cells. Elucidation of the mechanism by which H. pylori achieves HSP repression may prove to be beneficial in the identification of novel mechanisms to inhibit the HSR pathway and provide further insight into the interactions between H. pylori and the host gastric epithelium.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia.|Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Lang
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia.|Infection and Immunity, and Cancer Programs, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, 3800, Victoria, Australia.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Gorrell
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia.
authors.forename: Mona
authors.initials: M
authors.lastname: Tafreshi
authors.affiliation: Division of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo, 113-0033, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatakeyama
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia. terry.kwok@monash.edu.|Infection and Immunity, and Cancer Programs, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, 3800, Victoria, Australia. terry.kwok@monash.edu.
authors.forename: Terry
authors.initials: T
authors.lastname: Kwok
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Victoria, Australia. john.price@vu.edu.au.|Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, St Albans, Melbourne, VIC, Australia. john.price@vu.edu.au.
authors.forename: John T
authors.initials: JT
authors.lastname: Price
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D018869:Heat-Shock Response / Q000235:genetics; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D013274:Stomach Neoplasms / Q000150:complications / Q000235:genetics / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; C080866:cagA protein, Helicobacter pylori
keywords: CagA; Gastric cancer; Heat shock proteins; Heat shock response; Helicobacter pylori