The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression.
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.
['Lang|Ben J|BJ|', 'Gorrell|Rebecca J|RJ|', 'Tafreshi|Mona|M|', 'Hatakeyama|Masanori|M|', 'Kwok|Terry|T|', 'Price|John T|JT|']
D000942:Antigens, Bacterial D001426:Bacterial Proteins D005786:Gene Expression Regulation D057809:HEK293 Cells D006360:Heat-Shock Proteins D018869:Heat-Shock Response D016481:Helicobacter Infections D016480:Helicobacter pylori D054884:Host-Pathogen Interactions D006801:Humans D013274:Stomach Neoplasms
Helicobacter pylori CagA Heat shock proteins Heat shock response Gastric cancer