Inhibition of heat shock protein expression by Helicobacter pylori

Axsen, Wendy S.; Styer, Cathy M.; Solnick, Jay V.

doi:10.1016/j.micpath.2009.08.002

Cited by 25 publications

(36 citation statements)

References 38 publications

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“…However, these strains also harbor hopI1; it is possible that the increased susceptibility occurs through a HopI1-dependent mechanism. Hsp70 is a common target of plant and animal pathogens, which either exploit Hsp70 activity or suppress it (20,21,32,33). A central goal will be to discern the mechanism by which Hsp70 participates in interactions with different pathogens (identify client proteins and cellular processes that involve Hsp70) that influence the outcome of an infection.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas syringae hijacks plant stress chaperone machinery for virulence

Jeleńska

Hal²,

Greenberg³

2010

Proc. Natl. Acad. Sci. U.S.A.

153

131

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Plant heat shock protein Hsp70 is the major target of HopI1, a virulence effector of pathogenic Pseudomonas syringae. Hsp70 is essential for the virulence function of HopI1. HopI1 directly binds Hsp70 through its C-terminal J domain and stimulates Hsp70 ATP hydrolysis activity in vitro. In plants, HopI1 forms large complexes in association with Hsp70 and induces and recruits cytosolic Hsp70 to chloroplasts, the site of HopI1 localization. Deletion of a central P/Q-rich repeat region disrupts HopI1 virulence but not Hsp70 interactions or association with chloroplasts. Thus, HopI1 must not only bind Hsp70 through its J domain, but likely actively affects Hsp70 activity and/or specificity. At high temperature, HopI1 is dispensable for P. syringae pathogenicity, unless excess Hsp70 is provided. A working hypothesis is that Hsp70 has a defense-promoting activity(s) that HopI1 or high temperature can subvert. Enhanced susceptibility of Hsp70-depleted plants to nonpathogenic strains of P. syringae supports a defense-promoting role for Hsp70.T o cause a successful infection, many plant pathogenic bacteria use a type III secretion system through which dozens of different effector proteins are injected into plant cells (1). Pseudomonas syringae, a type III-requiring pathogen, causes disease on foliage and fruits of diverse plants. Some P. syringae effectors can restrict host range and/or disease potential, rendering the pathogen "avirulent," when they are recognized by a plant's defense machinery (2). However, in many cases, effectors suppress plant immune responses (1, 3). These virulence effectors are of intense interest, because their study not only gives insight into pathogenic mechanisms, but they can be used to identify previously unknown defense components (1, 4, 5) whose engineering may lead to novel approaches for creating disease-resistant plants.The P. syringae pv. maculicola ES4326 (Pma) HopI1 effector, a J protein (i.e., one that contains a J domain) suppresses accumulation of the defense regulator salicylic acid (SA) and related plant defenses (6). HopI1 localizes to chloroplasts where SA is synthesized (7) and also affects thylakoid stack structure within chloroplasts (6). HopI1-expressing plants can rescue the virulence defect of PmaΔhopI1 bacteria, indicating that HopI1 exerts its effects from within plant cells. All pathogenic P. syringae examined have a HopI1 allele with a conserved 190-amino acid N-terminal region of unknown function, a middle region with variable numbers of P/Q-rich 37/38 amino acid repeats (1-6) and a conserved 70-amino acid J domain. Several alleles with different repeat numbers can complement the virulence defect of PmaΔhopI1, indicating they all function similarly (6).The J domain of HopI1 provides a clue to HopI1's possible mechanism of action. J proteins bind Hsp70 through the J domain and stimulate Hsp70's ATP hydrolysis activity as well as other activities such as de novo folding of client proteins, intervening when proteins are improperly folded-often during stress conditions...

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Section: Discussionmentioning

confidence: 99%

Pseudomonas syringae hijacks plant stress chaperone machinery for virulence

Jeleńska

Hal²,

Greenberg³

2010

Proc. Natl. Acad. Sci. U.S.A.

153

131

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“…Given that CagA is one of the major virulence factors of H. pylori and the sole known protein delivered by the cagPAIencoded T4SS into the host cell during infection, we investigated the importance of CagA for the altered HSP expression previously observed upon H. pylori infection in vitro (Axsen et al 2009;Baek et al 2004;Konturek et al 2001;Pierzchalski et al 2006;Targosz et al 2006;Yeo et al 2004). Wild-type H. pylori strain P12 (P12wt) and its CagAdeficient isogenic mutant (P12ΔcagA) were used to infect the gastric adenocarcinoma cell line AGS to model H. pylori infection of gastric epithelia in vitro (Backert et al 2001;Kwok et al 2002;Kwok et al 2007).…”

Section: H Pylori-mediated Repression Of Host Hsps Expression Is Cagmentioning

confidence: 99%

“…Most bacterial infections studied to date induce HSP expression with numerous studies showing activation of the HSR upon infection by bacterial pathogens such as S. typhimurium, L. pneumophila, E. coli, and S. aureus (Axsen et al 2009;Shen et al 2009;Zheng et al 2004). In contrast to the upregulation of host-cell HSP expression associated with such bacterial infections, the gastric pathogen, Helicobacter pylori, has a novel ability to down-modulate host HSP expression upon acute infection of gastric epithelial cells (Axsen et al 2009;Baek et al 2004;Konturek et al 2001;Pierzchalski et al 2006;Targosz et al 2006;Yeo et al 2004).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to the upregulation of host-cell HSP expression associated with such bacterial infections, the gastric pathogen, Helicobacter pylori, has a novel ability to down-modulate host HSP expression upon acute infection of gastric epithelial cells (Axsen et al 2009;Baek et al 2004;Konturek et al 2001;Pierzchalski et al 2006;Targosz et al 2006;Yeo et al 2004). H. pylori is a Gram-negative, spiral bacterium that infects 50 % of humans globally.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have demonstrated complex activation of host signaling pathways by translocated CagA involving both CagA EPIYA phosphorylation-dependent and -independent mechanisms (Backert et al 2010). To date, the bacterial factors responsible for the repression of HSP expression upon acute H. pylori infection in vitro remains unclear, with previous studies providing evidence both for and against a potential role for CagA in mediating this effect (Axsen et al 2009;Targosz et al 2006). This study seeks to examine the underlying mechanisms by which H. pylori represses HSP expression.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression

Lang

Gorrell

Tafreshi

et al. 2016

Cell Stress and Chaperones

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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.

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HSP70 expression: does it a novel fatigue signalling factor from immune system to the brain?

Heck

Schöler

Bittencourt

2011

Cell Biochemistry & Function

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Integrative physiology studies have shown that immune system and central nervous system interplay very closely towards behavioural modulation. Since the 70-kDa heat shock proteins (HSP70s), whose heavy expression during exercise is well documented in the skeletal muscle and other tissues, is also extremely well conserved in nature during all evolutionary periods of species, it is conceivable that HSP70s might participate of physiologic responses such as fatigue induced by some types of physical exercise. In this way, increased circulating levels of extracellular HSP70 (eHSP70) could be envisaged as an immunomodulatory mechanism induced by exercise, besides other chemical messengers (e.g. cytokines) released during an exercise effort, that are able to binding a number of receptors in neural cells. Studies from this laboratory led us to believe that increased levels of eHSP70 in the plasma during exercise and the huge release of eHSP70 from lymphocytes during high-load exercise bouts may participate in the fatigue sensation, also acting as a danger signal from the immune system.

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Inhibition of heat shock protein expression by Helicobacter pylori

Cited by 25 publications

References 38 publications

Pseudomonas syringae hijacks plant stress chaperone machinery for virulence

Pseudomonas syringae hijacks plant stress chaperone machinery for virulence

The Helicobacter pylori cytotoxin CagA is essential for suppressing host heat shock protein expression

HSP70 expression: does it a novel fatigue signalling factor from immune system to the brain?

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