Methicillin Resistant Staphylococcus

Aureus

Barbara Jennings-Spring
Seminar in Molecular Biology 360
Smith College

What Is MRSA?
MRSA
Is

is Methicillin Resistant Staphylococcus aureus

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

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/AttackOfThe
Superbugs

Summary of Virulence
Determinants Of Staphylococcus
aureus

http://textbookofbacteriology.net/
staph.html

http://textbookofbacteriology.net/staph.html

Virulence Factors: Avoiding Host Defenses

Cell Wall

Cytoplasmic membrane- Osmotic barrier prevents

disequilibrium of ionic content. P reventing 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 antibacterial 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

www.med.sc.edu:85/ fox/staphimpetigo.jpg

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?

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