Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling

Bentley, Colette Cywes; Håkansson, Anders P.; Christianson, Jennifer; Wessels, Michael R.

doi:10.1111/j.1462-5822.2005.00525.x

Cited by 62 publications

(77 citation statements)

References 16 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stachybotrys chartarum toxin induced apoptosis in murine alveolar macrophages involved the gene expression of caspase-related genes (35). Although some other streptococcal virulence factors have been reported to be involved in apoptosis, their mode of action is less clear (38,39). It is not known how they may interact with the pathways presented in this study.…”

Section: Discussionmentioning

confidence: 45%

Procaspase 8 and Bax Are Up-regulated by Distinct Pathways in Streptococcal Pyrogenic Exotoxin B-induced Apoptosis

Chang

Tsai

Chuang

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have previously identified integrin ␣ v ␤ 3 and Fas as receptors for the streptococcal pyrogenic exotoxin B (SPE B), and G308S, a mutant of SPE B that binds to Fas only. In the current study we found that after binding to ␣ v ␤ 3 , SPE B stimulated the tyrosine phosphorylation of JAK2 and STAT1. STAT1 tyrosine phosphorylation was inhibited by a JAK2 inhibitor, AG490, short interfering RNA (siRNA) silencing of JAK2, and anti-␣ V ␤ 3 antibody. AG490 also decreased the binding of tyrosine-phosphorylated STAT1 to the procaspase 8 promoter, decreasing procaspase 8 expression, suggesting that SPE B up-regulates procaspase 8 expression via the JAK2/STAT1 pathway. Alternatively, both SPE B and G308S increased STAT1 phosphorylation at serine 727, which was inhibited by anti-Fas antibody, a p38 inhibitor, SB203580, and siRNA silencing of p38. In addition, SPE B and G308S increased binding of serine-phosphorylated STAT1 to the Bax promoter and Bax expression, which was decreased by SB203580. SPE B and G308S-stimulated Bax expression was also inhibited by anti-Fas antibody. These findings suggest that Fas mediate SPE B-induced Bax expression through p38. Silencing of JAK2 or p38 by siRNA blocked procaspase 8 expression, whereas only p38 siRNA decreased Bax expression. Furthermore, JAK2 inhibition and p38 inhibition reduced SPE B-induced apoptosis, but only p38 inhibition blocked G308S-induced apoptosis.

show abstract

Section: Discussionmentioning

confidence: 45%

Procaspase 8 and Bax Are Up-regulated by Distinct Pathways in Streptococcal Pyrogenic Exotoxin B-induced Apoptosis

Chang

Tsai

Chuang

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Host cell apoptosis very often facilitates the bacterial attack of the host and gaining access to the tissue (15). It has been shown previously that caspase-1, which is both proapoptotic and proinflammatory, is essential for S. Typhimurium to efficiently colonize the ceca and Peyer's patches and subsequently cause systemic typhoid-like disease in mice (42).…”

Section: Discussionmentioning

confidence: 99%

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

Kum

2011

Infect Immun

View full text Add to dashboard Cite

The Salmonella effector protein SopB has previously been shown to induce activation of Akt and protect epithelial cells from apoptosis in vitro. To characterize the role of Akt2 in host defense against Salmonella enterica serovar Typhimurium infection, wild-type (WT) mice and mice lacking Akt2 (Akt2 knockout [KO] mice) were infected using a Salmonella acute gastroenteritis model. Infected Akt2 KO mice showed a more pronounced morbidity and mortality associated with higher bacterial loads in the intestines and elevated levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-␣), gamma interferon (IFN-␥), and MCP-1, in the colons at 1 day postinfection compared to those shown in WT mice. Histopathological assessment and immunohistochemical analysis of cecal sections at 1 day postinfection revealed more severe inflammation and higher levels of neutrophil infiltration in the ceca of Akt2 KO mice. Flow cytometry analysis further confirmed an increase in the recruitment of Gr-1 ؉ CD11b ؉ neutrophils and F4/80 ؉ CD11b ؉ macrophages in the intestines of infected Akt2 KO mice. Additionally, enhanced levels of annexin V ؉ and terminal transferase dUTP nick end labeling-positive (TUNEL ؉ ) apoptotic cells in the intestines of infected Akt2 KO mice were also observed, indicating that Akt2 plays an essential role in protection against apoptosis. Finally, the differences in bacterial loads and cecal inflammation in WT and Akt2 KO mice infected with WT Salmonella were abolished when these mice were infected with the sopB deletion mutant, indicating that SopB may play a role in protecting the mice from Salmonella infection through the activation of Akt2. These data demonstrate a definitive phenotypic abnormality in the innate response in mice lacking Akt2, underscoring the important protective role of Akt2 in Salmonella infection.

show abstract

“…Over the past several decades, the molecular mechanisms underlying the adherence and internalization of GAS to epithelial cells as well as their intricate interactions have been extensively studied (8 -12). Although it was considered that most internalized GAS organisms are eliminated by intracellular killing, massive internalization or adherence of GAS preferentially induces programmed cell death of epithelial cells (13)(14)(15). These processes may lead to exposure of underlying tissues or cause damage to epithelium, providing GAS with a route to deeper tissues (intracellular route).…”

mentioning

confidence: 99%

Streptolysin S Contributes to Group A Streptococcal Translocation across an Epithelial Barrier

Sumitomo

Nakata

Higashino

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Group A Streptococcus pyogenes (GAS) is a human pathogen that causes local suppurative infections and severe invasive diseases. Systemic dissemination of GAS is initiated by bacterial penetration of the epithelial barrier of the pharynx or damaged skin. To gain insight into the mechanism by which GAS penetrates the epithelial barrier, we sought to identify both bacterial and host factors involved in the process. Screening of a transposon mutant library of a clinical GAS isolate recovered from an invasive episode allowed identification of streptolysin S (SLS) as a novel factor that facilitates the translocation of GAS. Of note, the wild type strain efficiently translocated across the epithelial monolayer, accompanied by a decrease in transepithelial electrical resistance and cleavage of transmembrane junctional proteins, including occludin and E-cadherin. Loss of integrity of intercellular junctions was inhibited after infection with a deletion mutant of the sagA gene encoding SLS, as compared with those infected with the wild type strain. Interestingly, following GAS infection, calpain was recruited to the plasma membrane along with E-cadherin. Moreover, bacterial translocation and destabilization of the junctions were partially inhibited by a pharmacological calpain inhibitor or genetic interference with calpain. Our data indicate a potential function of SLS that facilitates GAS invasion into deeper tissues via degradation of epithelial intercellular junctions in concert with the host cysteine protease calpain.

show abstract

Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling

Cited by 62 publications

References 16 publications

Procaspase 8 and Bax Are Up-regulated by Distinct Pathways in Streptococcal Pyrogenic Exotoxin B-induced Apoptosis

Procaspase 8 and Bax Are Up-regulated by Distinct Pathways in Streptococcal Pyrogenic Exotoxin B-induced Apoptosis

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

Streptolysin S Contributes to Group A Streptococcal Translocation across an Epithelial Barrier

Contact Info

Product

Resources

About