Methicillin Resistant Staphylococcus Aureus

Barbara Jennings-Spring Seminar in Molecular Biology 360 Smith College

What Is MRSA?
MRSA is Methicillin Resistant Staphylococcus aureus

Is a bacteria that is resistant to a synthetic penicillinmethicillin.

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

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

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

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???

History Of S aureus Resistance

The Basic Characteristics Of S aureus

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/ web8/mrsa.htm

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

Horizontal Gene Transfer-Another Mechanism For Resistance

http://www.bioteach.ubc.ca/Biodiversity/AttackOfTh eSuperbugs

Summary of Virulence Determinants Of

Staphylococcus aureus

http://textbookofbacteriology.net/sta ph.html

http://textbookofbacteriology.net/staph.html

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 hosts cell membranes Protein A- Immunological disguise.

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

Damage To The Host: Extracellular Products

Leukocidins-Kills White blood cells (WBCS) 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 Nasal carriage most common Hospitals *Dirty hands, towels, and daycare Airborne????? Community

Predisposing Factors Of Susceptibility

Integument injury Burns and trauma Foreign objects A history of chronic Infections Hormonal changes and stress Immunocompromised

Clinical Manifestations Of MRSA

A localized, superficial abscess or 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

Systemic S aureus In the Lower spine

Systemic Menstrual Toxic Shock

By MRSA

Most major organs fail with disseminated MRSA (TSS-1)

www.web.net/terrafemme/ cashnightmare.htm

How Accurate Can Your Diagnosis Of MRSA Be?

TABLE 1. Comparison of the levels of accuracy of reactions of S. aureus isolates on CHROMagar Staph aureus, DNase, and MSA and of coagulase testing of CoNS after 18 to 24 h of incubation % of isolates showing positive reactions Identification method S. aureus (n = 114) CHROMagar Staph aureus DNase MSA Coagulaseb
a

Accuracy of medium in discriminating S. aureus and CoNS Sensitivity (%) Specificity (%) 100 98.0 98.0 100 100 95.4 63.5 100

CoNS (n = 22) 0a 4.6 36.5 0

100 98.0 98.0 100

S. chromogenes produced a natural carotenoid (orange or red) pigment and gave a slightly pink color. The isolate was identified by API20 Staph. b All coagulase testing was confirmed by the standard tube method.

http://jcm.asm.org/cgi/content/full/38/6/2378

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)

Biotechnology: Drugs In Development

Oritavancin-Binds to normal cell wall precursors Tigecyclin-Works on efflux pumps Dalbavancin- Bacteriacidal

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.

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)

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

The Real Cost Of Infectious Diseases

Rising Rates Of Resistant Bacterial Infections=Rising Budget

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

Thats All Folks!! Any Questions????

Staph

cells attaching photo courtesy of Dr. Sharon Peacock- University of Oxford

References

1 Mitchell, David.MRSA.whats 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. 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/fsStaphVAX.pdf