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Methicillin Resistant Staphylococcus Aureus

Methicillin Resistant Staphylococcus Aureus

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Methicillin Resistant Staphylococcus Aureus

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  1. Methicillin Resistant Staphylococcus Aureus Barbara Jennings-Spring Seminar in Molecular Biology 360 Smith College

  2. What Is MRSA? • MRSA is “Methicillin Resistant Staphylococcus aureus • Is a bacteria that is resistant to a synthetic penicillin- methicillin. • MRSA causes a variety of disseminated, lethal infections in humans. • Has the ability to easily transfer resistant genes to other species directly and indirectly • Overuse of antibiotics imposes selective pressures which mediates the acquisition of resistance

  3. Objective To gain a broader understanding of the resistance mechanisms and virulence factors involved with MRSA and how this disease impacts on a physical and global level

  4. Research • History of MRSA • The basic Biology of Staphylococcus aureus • Molecular Basis For Virulence factors And Resistance • Clinical Presentation Of Disease • Detection Of pathogen • Biotechnology Treatments • Public Health Strategies • Political And Social Consequences

  5. A Timeline Of Antibiotic Resistance • 1941 Penicillin • 1943 Streptomycin • 1945 Cephalosporins • 1950 Tetracycline • 1952 Erythromycin • 1956 Vancomycin • 1960 Methicillin • 1962 Lincomycin • 1962 Quinolones • 1970 Penems • 1980 Monobactams • 2010 Could this be the end of an antibiotic era???

  6. History Of S aureus Resistance

  7. The Basic Characteristics Of S aureus • Gram positive • Non-motile • Spherical • Grows in chains • Resembles clumps of grapes • Golden color • Hemolytic pattern on blood agar • Produces coagulase and catalase enzymes img/staph_em.jpg www.aic.cuhk.edu.hk/ web8/mrsa.htm

  8. Mechanism Of Resistance • http://www.jci.org/cgi/content/full/114/12/1693/F1 http://www.jci.org/cgi/content/full/114/12/1693/F1

  9. Horizontal Gene Transfer-Another Mechanism For Resistance http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs

  10. Summary of Virulence Determinants Of Staphylococcus aureus • http://textbookofbacteriology.net/staph.html http://textbookofbacteriology.net/staph.html

  11. Virulence Factors: Avoiding Host Defenses • Cell Wall • Cytoplasmic membrane- Osmotic barrier prevents disequilibrium of ionic content. Preventing cell osmotic instability and susceptibility to lysis • Polysaccharide capsule-slime layer; adhesin. Inhibits phagocytosis • Petidoglycan-Allows bacteria to attach host’s cell membranes • Protein A- Immunological disguise.

  12. Invasive enzymes • Coagulase Complex-Seals off infection, preventing phagocytic engulfment • Protease, lipase, & DNase provide nourishment for MRSA bacterium • FAME-(Fatty acid modifying enzyme) modifies the anti-bacterial lipids side chain-inactivating antibiotic action • Staphylokinase-Fibrinolysisn aids the in spreading factor • Hyaluronidase- Destroys connective tissue

  13. Damage To The Host: Extracellular Products • Leukocidins-Kills White blood cells (WBC’S) • Alpha, Beta, Delta toxins-These damaging toxins bid to to cell wall surface, forms a pore, and cellular machinery of host cell leak out

  14. Source Of MRSA Infections • Some infections are caused by own epithelial flora-self contamination • Nasal carriage most common • Hospitals • *Dirty hands, towels, and daycare • Airborne????? • Community

  15. Predisposing Factors Of Susceptibility • Integument injury • Burns and trauma • Foreign objects • A history of chronic Infections • Hormonal changes and stress • Immunocompromised

  16. Clinical Manifestations Of MRSA • A localized, superficial abscess or • Invasion of lymphatics, blood, and major organs

  17. Superficial Infections

  18. Scalded Skin Syndrome: Classic Toxic Shock www.aafp.org/afp/ 20000815/804.html

  19. S. aureus Impetigo www.med.sc.edu:85/ fox/staph-impetigo.jpg

  20. Systemic S aureus In the Lower spine • .

  21. Systemic Menstrual Toxic Shock By MRSA • Most major organs fail with disseminated MRSA (TSS-1) www.web.net/terrafemme/ cashnightmare.htm

  22. How Accurate Can Your Diagnosis Of MRSA Be? http://jcm.asm.org/cgi/content/full/38/6/2378

  23. Biotechnology: Current Drug Treatments For MRSA • MRSA Drugs of Choice:  • Linezolid-Protein synthesis inhibitor Daptomycin-Causes membrane depolarization in bacteria-so no membrane transport • Vancomycin-Acts by interfering with the construction of cell wall. Still works well with other antibiotics • Alternatives:  Synercid, Rifampin • Third-Line agents:  TMP-SMX (Sulfa)

  24. Biotechnology: Drugs In Development • Oritavancin-Binds to normal cell wall precursors • Tigecyclin-Works on efflux pumps • Dalbavancin- Bacteriacidal

  25. Biotechnology: A Novel Vaccination For S Aureus • Development of StaphVAX®, a polysaccharide conjugate vaccine against S. aureus infections • The results of the phase 3 clinical trials of the vaccine (Staph VAX) will be presented 2006 according to the NIH.

  26. Public Health Response and CDC • Technical help for healthcare professionals • National program of surveillance • Evidence-based educational campaigns • National resource library • Researching S. aureus toxins • More info? Go to www.cdc.goc (CDC,2005)

  27. Prevention • Draining infections must be kept covered • Talk to your physician about wound management techniques • Wash hands frequently with soap and water • Avoid sharing personal items • Wipe objects down with alcohol. • Advise health care workers to wash their hands before touching you or your hospital equipment

  28. The Real Cost Of Infectious Diseases

  29. Rising Rates Of Resistant Bacterial Infections=Rising Budget

  30. Summary • Multiple MRSA isolates are circulating in your local hospital and community • MRSA has many mechanisms resistance and virulence factors • MecA gene is the gene responsible for methicillin resistance • Many of the MRSA isolates are encoded with the Sccmec mobile element in them • MRSA must be isolated and treated aggressively to prevent secondary infections and spread

  31. That’s All Folks!! Any Questions???? • Staph cells attaching photo courtesy of Dr. Sharon Peacock- University of Oxford

  32. References • 1 Mitchell, David.MRSA.”what’s New”. Inoculum. Volume 8, number 2 (1999) 1-12. • 2 textbookofbacteriology.net/resantimicrobial.html • 3 healthsciences.columbia.edu/ dept/ps/2007/mid/2006/transcript_02_mid22.pdf • 4 http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs • 5. Foster, Timothy. The staphylococcus aureus “superbug”.J. clin Ivestigation • Volume number114 (2004) 1693-1696. • 6. www.channing.harvard.edu/4a.htm • 7. ww.ncbi.nlm.nih.gov. • 8. www.aafp.org/afp/ 20000815/804.html • 9. Journal of Clinical Microbiology, June 2000, p. 2378-2380, Vol. 38, No. 60095-1137/04.00+0 • 10. www.FDA.com (FDA archives) • 11.www.postgradmed.com/issues/2001/10_01/hoel.htm12. www.cdc.gov/ncidod/hip/aresist/mrsa_CDCactions.htm • 13. www.medscape.com • 14 http://www.nabi.com/images/factsheets/fsStaphVAX.pdf