The tst gene associated Staphylococcus aureus pathogenicity island facilitates its pathogenesis by promoting the secretion of inflammatory cytokines and inducing immune suppression

Aim. Study of the effect of exopolysaccharides (EPS) of lactic acid cocci on cytokine activity of macrophages of mice with phagocytosis in vitro Staphylococcus aureus 209-P. Materials and methods. The EPS of Streptococcus thermophilus and Lactococcus lactis B-1662 was used in the work. At 13, 5 and 7, AMP and PMP were isolated and the phagocytosis process was modeled in vitro. After 30 minutes, 1, 6 and 24 hours, the content of pro-inflammatory cytokines IL-1a and TNF-a was determined. Results. EPSs had an ambiguous effect on the production of cytokines. The greatest effect on the synthesis was provided by EPS of S. thermophilus. Conclusion. The results of the study allow us to talk about the possibility of using EPS of S. thermophilus as a preventive immunomodulator for correction of the cytokine status of animals.

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Characterization of a Putative Pathogenicity Island from Bovine Staphylococcus aureus Encoding Multiple Superantigens

Journal of Bacteriology ◽

10.1128/jb.183.1.63-70.2001 ◽

2001 ◽

Vol 183 (1) ◽

pp. 63-70 ◽

Cited By ~ 193

Author(s):

J. Ross Fitzgerald ◽

Steven R. Monday ◽

Timothy J. Foster ◽

Gregory A. Bohach ◽

Patrick J. Hartigan ◽

...

Keyword(s):

Staphylococcus Aureus ◽

T Cells ◽

Integration Site ◽

Random Amplified Polymorphic Dna ◽

Molecular Genetic ◽

Pathogenicity Island ◽

Molecular Genetic Analysis ◽

Deletion Event ◽

Allele Replacement

ABSTRACT Previous studies have demonstrated that a proportion ofStaphylococcus aureus isolates from bovine mastitis coproduce toxic shock syndrome toxin (TSST) and staphylococcal enterotoxin C (SEC). In this study, molecular genetic analysis of one such strain, RF122, revealed the presence of a 15,891-bp putative pathogenicity island (SaPIbov) encoding the genes for TSST (tst), the SEC bovine variant (sec-bovine), and a gene (sel) which encodes an enterotoxin-like protein. The island contains 21 open reading frames specifying hypothetical proteins longer than 60 amino acids including an integrase-like gene. The element is bordered by 74-bp direct repeats at the left and right junctions, and the integration site lies adjacent to the 3′ end of the GMP synthase gene (gmps) in the S. aureuschromosome. SaPIbov contains a central region of sequence identity with the previously characterized tst pathogenicity island SaPI1 (J. A. Lindsay et al., Mol. Microbiol. 29:527–543, 1998). A closely related strain, RF120, of the same multilocus enzyme electrophoretic type, random amplified polymorphic DNA type, and ribotype, does not contain the island, implying that the element is mobile and that a recent insertion/deletion event has taken place. TSST and TSST/SEC-deficient mutants of S. aureus strain RF122 were constructed by allele replacement. In vitro bovine Vβ-specific lymphocyte expansion analysis by culture supernatants of wild-type strains and of tst and sec-bovine allele replacement mutants revealed that TSST stimulates BTB13-specific T cells whereas SEC-bovine stimulates BTB93-specific T cells. This suggests that the presence of SaPIbov may contribute to modulation of the bovine immune response.

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Staphylococcus aureus α-Toxin Induces Inflammatory Cytokines via Lysosomal Acid Sphingomyelinase and Ceramides

Cellular Physiology and Biochemistry ◽

10.1159/000484296 ◽

2017 ◽

Vol 43 (6) ◽

pp. 2170-2184 ◽

Cited By ~ 15

Author(s):

Jie Ma ◽

Erich Gulbins ◽

Michael J. Edwards ◽

Charles C. Caldwell ◽

Martin Fraunholz ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Confocal Microscopy ◽

Inflammatory Cytokines ◽

Cathepsin B ◽

Molecular Mechanisms ◽

Ex Vivo ◽

Clinical Problem ◽

Acid Sphingomyelinase ◽

Tnf Α ◽

Factor Α

Background/Aims: Staphylococcus aureus (S. aureus) infections are a major clinical problem and range from mild skin and soft-tissue infections to severe and even lethal infections such as pneumonia, endocarditis, sepsis, osteomyelitis, and toxic shock syndrome. Toxins that are released from S. aureus mediate many of these effects. Here, we aimed to identify molecular mechanisms how α-toxin, a major S. aureus toxin, induces inflammation. Methods: Macrophages were isolated from the bone marrow of wildtype and acid sphingomyelinase-deficient mice, stimulated with S. aureus α-toxin and activation of the acid sphingomyelinase was quantified. The subcellular formation of ceramides was determined by confocal microscopy. Release of cathepsins from lysosomes, activation of inflammasome proteins and formation of Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were analyzed by western blotting, confocal microscopy and ELISA. Results: We demonstrate that S. aureus α-toxin activates the acid sphingomyelinase in ex vivo macrophages and triggers a release of ceramides. Ceramides induced by S. aureus α-toxin localize to lysosomes and mediate a release of cathepsin B and D from lysosomes into the cytoplasm. Cytosolic cathepsin B forms a complex with Nlrc4. Treatment of macrophages with α-toxin induces the formation of IL-1β and TNF-α. These events are reduced or abrogated, respectively, in cells lacking the acid sphingomyelinase and upon treatment of macrophages with amitriptyline, a functional inhibitor of acid sphingomyelinase. Pharmacological inhibition of cathepsin B prevented activation of the inflammasome measured as release of IL-1β, while the formation of TNF-α was independent of cathepsin B. Conclusion: We demonstrate a novel mechanism how bacterial toxins activate the inflammasome and mediate the formation and release of cytokines: S. aureus α-toxin triggers an activation of the acid sphingomyelinase and a release of ceramides resulting in the release of lysosomal cathepsin B and formation of pro-inflammatory cytokines.

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