Transcript Methicillin Resistant Staphylococcus Aureus

Methicillin Resistant Staphylococcus Aureus
Barbara Jennings-Spring
Seminar in Molecular Biology 360
Smith College
What Is MRSA?
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MRSA is “Methicillin Resistant Staphylococcus aureus
Is a bacteria that is resistant to a synthetic penicillinmethicillin.
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MRSA causes a variety of disseminated, lethal infections
in humans.
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Has the ability to easily transfer resistant genes to other
species directly and indirectly
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Overuse of antibiotics imposes selective pressures which
mediates the acquisition of resistance
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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
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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
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1941 Penicillin
1943 Streptomycin
1945 Cephalosporins
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1950 Tetracycline
1952 Erythromycin
1956 Vancomycin
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1960 Methicillin
1962 Lincomycin
1962 Quinolones
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1970 Penems
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1980 Monobactams
2010 Could this be the end of an antibiotic era???
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History Of S aureus Resistance
The Basic Characteristics Of S aureus
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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
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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
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http://textbookofbacteriology.net/stap
h.html
http://textbookofbacteriology.net/staph.html
Virulence Factors: Avoiding Host Defenses
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Cell Wall
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Cytoplasmic membrane- Osmotic barrier prevents
disequilibrium of ionic content. Preventing cell osmotic
instability and susceptibility to lysis
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Polysaccharide capsule-slime layer; adhesin. Inhibits
phagocytosis
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Petidoglycan-Allows bacteria to attach host’s cell
membranes
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Protein A- Immunological disguise.
Invasive enzymes
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Coagulase Complex-Seals off infection, preventing
phagocytic engulfment
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Protease, lipase, & DNase provide nourishment for MRSA
bacterium
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FAME-(Fatty acid modifying enzyme) modifies the anti-bacterial
lipids side chain-inactivating antibiotic action
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Staphylokinase-Fibrinolysisn aids the in spreading factor
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Hyaluronidase- Destroys connective tissue
Damage To The Host: Extracellular Products
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Leukocidins-Kills White blood cells (WBC’S)
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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
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Predisposing Factors Of
Susceptibility
Integument injury
 Burns and trauma
 Foreign objects
 A history of chronic Infections
 Hormonal changes and stress
 Immunocompromised
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Clinical Manifestations Of MRSA
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A localized, superficial abscess or
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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
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Systemic Menstrual Toxic Shock
By MRSA
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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
CHROMagar Staph
aureus
DNase
MSA
Coagulaseb
Accuracy of medium in
discriminating S. aureus and
CoNS
S. aureus
(n = 114)
CoNS
(n = 22)
100
0a
100
100
98.0
98.0
100
4.6
36.5
0
98.0
98.0
100
95.4
63.5
100
Sensitivity (%) Specificity (%)
a
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:
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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
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Biotechnology: A Novel Vaccination For
S Aureus
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Development of StaphVAX®, a
polysaccharide conjugate vaccine
against S. aureus infections
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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
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Technical help for healthcare professionals
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National program of surveillance
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Evidence-based educational campaigns
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National resource library
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Researching S. aureus toxins
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More info? Go to www.cdc.goc
(CDC,2005)
Prevention
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Draining infections must be kept covered
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Talk to your physician about wound management techniques
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Wash hands frequently with soap and water
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Avoid sharing personal items
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Wipe objects down with alcohol.
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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
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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
That’s All Folks!! Any
Questions????
Staph
cells attaching photo courtesy of Dr. Sharon
Peacock- University of Oxford
References
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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. 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