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Autoinducer of Virulence As a Target for Vaccine and Therapy Against Staphylococcus aureus

Autoinducer of Virulence As a Target for Vaccine and Therapy Against Staphylococcus aureus. Vasiliki Papadimitriou Seminar February 21, 2000. Purpose and Rationale. To find a new approach to treating and vaccinating S. aureus infections via autoinducer of virulence

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Autoinducer of Virulence As a Target for Vaccine and Therapy Against Staphylococcus aureus

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  1. Autoinducer of Virulence As a Target for Vaccine and Therapy Against Staphylococcus aureus Vasiliki Papadimitriou Seminar February 21, 2000

  2. Purpose and Rationale • To find a new approach to treating and vaccinating S. aureus infections via autoinducer of virulence • Motive behind finding a new approach is due to the development of drug-resistant bacteria

  3. Profile of S. aureus • Gram-positive pathogenic bacteria • responsible for: • toxic shock syndrome • septicemia • meningitis • endocarditis • pneumonia • enterotoxins • hemolysins

  4. Regulation of S. aureus • By regulatory RNA molecule, RNA III (encoded by agr locus) • autoinduced by RAP (RNA III activating protein) • only active at a threshold concentration • inhibited by RIP (RNA III inhibiting protein) • produced by a non-pathogenic bacteria mutated by nitrosoguanidine • Known not to be determined by the any codes of genes such as agr ( as shown in following experiment)

  5. Experiment • Replaced an agr-null strain with a tetM marker • Used murine model of cutaneous infection to test if S. aureus can be inhibited by using RAP to immunize • Determination of antibody development by immunoblotting and binding activity

  6. Inhibition of RAP by RIP and Pep

  7. RAP is independent of agr locus

  8. Results • RAP and RAP* had no real comparable differences in suppression of SD cells, however, were significantly more effective than the control CFA • According to Table 1, RIP has an immune effect in mice but has a smaller effect when almost double the amount of SD cells are used • After treating SD cells with Pep and RIP, in comparison with the controls of saline and DMSO, Pep had a significantly better effect on suppressing SD cells

  9. Results (cont’d) • Those treated with the RAP vaccine had developed antibodies • Controls did not develop antibodies • Some mice had preimmune antibodies to RAP • refer to Table 1 for discussion

  10. Conclusion • Pep had significant suppressive effects on SD cells at a high concentration • This ratio between the amount of bacteria and synthetic RIP helps determine the effectiveness of the host to fight the infection, and even more important the toxicity • Scientist believe this technique is potentially one of the new approaches to avoid the increased bacteria resistance to antibiotics

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