Methicillin Resistant Staphylococcus Aureus Barbara JenningsSpring Seminar in

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

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

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

Research n n n n n 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

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

History Of S aureus Resistance

The Basic Characteristics Of S aureus n n n n Gram positive Non-motile Spherical Grows in chains Resembles clumps of grapes img/staph_em. jpg Golden color Hemolytic pattern on blood agar Produces coagulase and catalase enzymes www. aic. cuhk. edu. hk/ web 8/mrsa. htm

Mechanism Of Resistance n http: //www. jci. org/cgi/content/full/114/12/1693/F 1

Horizontal Gene Transfer-Another Mechanism For Resistance http: //www. bioteach. ubc. ca/Biodiversity/Attack. Of. Th e. Superbugs

Summary of Virulence Determinants Of Staphylococcus aureus n http: //textbookofbacteriology. net/stap h. html http: //textbookofbacteriology. net/staph. html

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

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

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

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

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

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

Superficial Infections

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

S. aureus Impetigo www. med. sc. edu: 85/ fox/staphimpetigo. jpg

Systemic S aureus In the Lower spine n .

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

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

Biotechnology: Current Drug Treatments For MRSA n MRSA Drugs of Choice: n n 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)

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

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

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

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

The Real Cost Of Infectious Diseases

Rising Rates Of Resistant Bacterial Infections=Rising Budget

Summary n n n Multiple MRSA isolates are circulating in your local hospital and community MRSA has many mechanisms resistance and virulence factors Mec. A 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

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

References n n n n 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_mid 22. pdf 4 http: //www. bioteach. ubc. ca/Biodiversity/Attack. Of. The. Superbugs 5. Foster, Timothy. The staphylococcus aureus “superbug”. J. clin Ivestigation Volume number 114 (2004) 1693 -1696. 6. www. channing. harvard. edu/4 a. 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. 6 0095 -1137/04. 00+0 10. www. FDA. com (FDA archives) 11. www. postgradmed. com/issues/2001/10_01/hoel. htm 12. www. cdc. gov/ncidod/hip/aresist/mrsa_CDCactions. htm 13. www. medscape. com 14 http: //www. nabi. com/images/factsheets/fs. Staph. VAX. pdf