Staphylococcus aureusalpha-toxin induces apoptosis in peripheral blood mononuclear cells: role of endogenous tumour necrosis factor-alpha and the mitochondrial death pathway

Haslinger, Bettina; Strangfeld, Katrin; Peters, Georg; Schulze‐Osthoff, Klaus; Sinha, Bhanu

doi:10.1046/j.1462-5822.2003.00317.x

Cited by 97 publications

(101 citation statements)

References 55 publications

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“…These results are consistent with the eliminated transcription of hla expression in vitro in this study and previous reports (11,22). Our unpublished data and studies by other investigators have demonstrated that alpha-toxin is necessary for S. aureus to cause different types of cell apoptosis and death via different signaling transduction pathways (2,14,25,33). Furthermore, in this study we demonstrated that the SaeRS system plays an important role in S. aureus pathogenesis in a murine model of infection.…”

Section: Discussionsupporting

confidence: 93%

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

et al. 2006

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Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-component signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding ␣-, ␤-, and ␥-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells.

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Section: Discussionsupporting

confidence: 93%

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

et al. 2006

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“…Besides its capability to induce necrosis, ␣-toxin has been reported to generate, at subcytotoxic concentrations, small, monovalent cation-selective pores leading to cell activation and death through the activation of the intrinsic apoptotic pathway (1,12). We looked for features of apoptosis in cells exposed to S. aureus for periods shorter than 24 h. Excitingly, by two different approaches, we showed that at 8 h postinfection a high percentage of cells exhibited characteristics of apoptotic cells and that during S. aureus infection, cells entered in an apoptotic process that was rapidly followed by necrosis.…”

Section: Discussionmentioning

confidence: 99%

Dynamic interaction between airway epithelial cells andStaphylococcus aureus

Silva¹,

Zahm²,

Gras³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Staphylococcus aureus is a major cause of pulmonary infection, particularly in cystic fibrosis (CF) patients. However, few aspects of the interplay between S. aureus and host airway epithelial cells have been investigated thus far. We investigated by videomicroscopy the time- and bacterial concentration-dependent (104, 106, and 108CFU/ml) effect of S. aureus on adherence, internalization, and the associated damage of the airway epithelial cells. The balance between the secretion by S. aureus of the α-toxin virulence factor and by the airway cells of the antibacterial secretory leukoproteinase inhibitor (SLPI) was also analyzed. After 1 h of interaction, whatever the initial bacterial concentration, a low percentage of S. aureus (<8%) adhered to airway cells, and no airway epithelial cell damage was observed. In contrast, after 24 h of incubation, more bacteria adhered to airway epithelial cells, internalized bacteria were observed, and a bacterial concentration-dependent effect on airway cell damage was observed. At 24 h, most airway cells incubated with bacteria at 108CFU/ml exhibited a necrotic phenotype. The necrosis was preceded by a transient apoptotic process. In parallel, we observed a time- and bacterial concentration-dependent decrease in SLPI and increase in α-toxin expression. These results suggest that airway cells can defend against S. aureus in the early stages of infection. However, in later phases, there is a marked imbalance between the bactericidal capacity of host cells and bacterial virulence. These findings reinforce the potential importance of S. aureus in the pathogenicity of airway infections, including those observed early in CF patients.

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“…From our results, Alpha hemolysin protein had high inhibitory activity against HepG-2 and HCT-116, and had weak inhibitory activity against MCF-7 and A-549. In this connection, Haslinger et al (2003); Essmann et al (2003) had reported that S. aureus α-toxin is a pore-forming toxin that can caused apopotosis of tumor cells at higher concentrations. In this study, it was found that the cell viability of MCF-7 was represented 78.95% per 48 hours.…”

Section: Application Of Recombinant α-Hemolysin Protein In Different mentioning

confidence: 99%

Cloning and Expression of Alpha Hemolysin Toxin Gene of Staphylococcus aureus Against Human Cancer Tissue

Abdel-Fattah

Hafez

Zaki

et al. 2017

Int J Appl Sci Biotechnol

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Recombinant technology has crucial impact in therapy development. In microbial environment, Pathogenic bacteria such as Staphylococcus aureus produces alpha hemolysin protein. This protein is used as anticancer protein. In our study, alpha hemolysin toxin (hia) gene was isolated from S. aureus isolate. The isolate of S. aureus was isolated from blood samples of patients at Microbiology laboratory of Chlidren Mansoura Unversity Hospital. The purified PCR of hia gene of S. aureus strain was subjected to sequencing and cloning. Recombinant alpha hemolysin toxin cloning was detected by PCR, and α-hemolysin protein was purified by Sphadex. The purified α-protein was used as anticancer against HepG-2 cells (human Hepatocellular carcinoma), HCT-116 cells (human colon carcinoma), MCF-7 cells (human breast cancer cell line) and A-549 cells (human Lung cancer cell line).

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Staphylococcus aureusalpha-toxin induces apoptosis in peripheral blood mononuclear cells: role of endogenous tumour necrosis factor-alpha and the mitochondrial death pathway

Cited by 97 publications

References 55 publications

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

Dynamic interaction between airway epithelial cells andStaphylococcus aureus

Cloning and Expression of Alpha Hemolysin Toxin Gene of Staphylococcus aureus Against Human Cancer Tissue

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