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Methicillin Resistant

Methicillin

Resistant Staphylococcus

Staphylococcus

Aureus

Aureus

Barbara Jennings-Spring

Barbara

Jennings-Spring

Seminar inin Molecular

Seminar

Molecular Biology

Biology 360

360

Smith College

Smith

College

Methicillin Resistant Methicillin Resistant Staphylococcus Staphylococcus Aureus Aureus Barbara Jennings-Spring Barbara Jennings-Spring in in Molecular Seminar

What

What IsIs MRSA?

MRSA?

MRSA

MRSA isis “Methicillin

Methicillin Resistant

Resistant Staphylococcus

Staphylococcus aureus

aureus

IsIs aa bacteria

bacteria that

that isis resistant

resistant toto aa synthetic

synthetic penicillin-

penicillin- methicillin.

methicillin.

MRSA

MRSA causes

causes aa variety

variety of

of disseminated,

disseminated, lethal

lethal infections

infections inin

humans.

humans.

Has

Has the

the ability

ability toto easily

easily transfer

transfer resistant

resistant genes

genes toto other

other species

species

directly and

directly

and indirectly

indirectly

Overuse

Overuse of

of antibiotics

antibiotics imposes

imposes selective

selective pressures

pressures which

which mediates

mediates

the acquisition

the

acquisition of

of resistance

resistance

Objective

Objective

ToTo gain

gain aa broader

broader understanding

understanding of

of the

the resistance

resistance

mechanisms and

mechanisms

and virulence

virulence factors

factors involved

involved with

with MRSA

MRSA

and how

and

how this

this disease

disease impacts

impacts onon aa physical

physical and

and global

global

level

level

Objective Objective To To gain a a broader understanding of the resistance mechanisms and mechanisms and
Objective Objective To To gain a a broader understanding of the resistance mechanisms and mechanisms and

Research

Research

History

History of

of MRSA

MRSA

The

The basic

basic Biology

Biology of

of Staphylococcus

Staphylococcus aureus

aureus

Molecular

Molecular Basis

Basis For

For Virulence

Virulence factors

factors And

And

Resistance

Resistance

Clinical

Clinical Presentation

Presentation Of

Of Disease

Disease

Detection

Detection Of

Of pathogen

pathogen

Biotechnology

Biotechnology Treatments

Treatments

Public

Public Health

Health Strategies

Strategies

Political

Political And

And Social

Social Consequences

Consequences

AA Timeline

Timeline Of

Of Antibiotic

Antibiotic Resistance

Resistance

1941 Penicillin

1941

Penicillin

1943 Streptomycin

1943

Streptomycin

1945 Cephalosporins

1945

Cephalosporins

1950 TTetracycline

1950

etracycline

1952 Erythromycin

1952

Erythromycin

1956 Vancomycin

1956

Vancomycin

1960 Methicillin

1960

Methicillin

1962 Lincomycin

1962

Lincomycin

1962 Quinolones

1962

Quinolones

1970

1970 Penems

Penems

AA Timeline Of Antibiotic Resistance        1941 Penicillin 1941 Penicillin

1980 Monobactams

1980

Monobactams

2010 Could

2010

Could this

this bebe the

the end

end of

of anan antibiotic

antibiotic era???

era???

History Of

History

Of SS aureus

aureus

Resistance

Resistance

Of History SS aureus Resistance Resistance

The Basic

The

Basic Characteristics

Characteristics Of

Of SS

aureus

aureus

Gram Gram positive positive

Non-motile Non-motile

Spherical Spherical

Grows Grows inin chains chains

Basic The Characteristics Of SS aureus aureus  Gram Gram positive positive  Non-motile Non-motile

Resembles Resembles clumps clumps of of grapes grapes

Golden

Golden color

color

Hemolytic

Hemolytic pattern

pattern onon blood

blood agar

agar

img/staph_em.jpg
img/staph_em.jpg

Produces Produces coagulase coagulase and and catalase catalase enzymes enzymes

www.aic.cuhk.edu.hk/ web8/mrsa.htm

Mechanism Of

Mechanism

Of Resistance

Resistance

 http://www.jci.org/cgi/content/full/114/12/1693/F1 http://www.jci.org/cgi/content/full/114/12/1693/F1
http://www.jci.org/cgi/content/full/114/12/1693/F1
http://www.jci.org/cgi/content/full/114/12/1693/F1

http://www.jci.org/cgi/content/full/114/12/1693/F1

http://www.jci.org/cgi/content/full/114/12/1693/F1

Horizontal

Horizontal Gene

Gene Transfer-Another

Transfer-Another

Mechanism

Mechanism For

For Resistance

Resistance

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

http://www.bioteach.ubc.ca/Biodiversity/AttackOfThe

http://www.bioteach.ubc.ca/Biodiversity/AttackOfThe

Superbugs

Superbugs

Summary of

Summary

of Virulence

Virulence

Determinants Of

Determinants

Of Staphylococcus

Staphylococcus

aureus

aureus

 http://textbookofbacteriology.net/ http://textbookofbacteriology.net/ staph.html staph.html
 http://textbookofbacteriology.net/
http://textbookofbacteriology.net/
staph.html
staph.html

http://textbookofbacteriology.net/staph.html

http://textbookofbacteriology.net/staph.html

Virulence

Virulence Factors:

Factors: Avoiding

Avoiding Host

Host Defenses

Defenses

Cell

Cell Wall

Wall

Cytoplasmic membrane-

Cytoplasmic

disequilibrium of

disequilibrium

instability and

instability

of ionic

membrane- Osmotic

Osmotic barrier

barrier prevents

prevents

ionic content.

content. PPreventing

reventing cell

cell osmotic

osmotic

and susceptibility

susceptibility toto lysis

lysis

Polysaccharide capsule-slime

Polysaccharide

phagocytosis

phagocytosis

capsule-slime layer;

layer; adhesin.

adhesin. Inhibits

Inhibits

Petidoglycan-Allows bacteria

Petidoglycan-Allows

membranes

membranes

bacteria toto attach

attach host’s

hosts cell

cell

Protein

Protein A-

A- Immunological

Immunological disguise.

disguise.

Invasive

Invasive enzymes

enzymes

Coagulase

Coagulase Complex-Seals

phagocytic engulfment

phagocytic

engulfment

Complex-Seals offoff infection,

infection, preventing

preventing

Protease,

Protease, lipase,

MRSA bacterium

MRSA

bacterium

lipase, && DNase

DNase provide

provide nourishment

nourishment for

for

FAME-(Fatty acid

FAME-(Fatty

bacterial lipids

bacterial

acid modifying

modifying enzyme)

enzyme) modifies

modifies the

the anti-

anti-

lipids side

side chain-inactivating

chain-inactivating antibiotic

antibiotic action

action

Staphylokinase-Fibrinolysisn aids

Staphylokinase-Fibrinolysisn

factor

factor

aids the

the inin spreading

spreading

Hyaluronidase-

Hyaluronidase- Destroys

Destroys connective

connective tissue

tissue

Damage TToo The

Damage

The Host:

Host: Extracellular

Extracellular

Products

Products

Leukocidins-Kills

Leukocidins-Kills White

White blood

blood cells

cells

(WBC’S)

(WBC’S)

Alpha,

Alpha, Beta,

Beta, Delta

Delta toxins-These

toxins-These

damaging toxins

damaging

toxins bid

bid toto toto cell

cell wall

wall

surface, forms

surface,

forms aa pore,

pore, and

and cellular

cellular

machinery of

machinery

of host

host cell

cell leak

leak out

out

Source Of

Source

Of MRSA

MRSA Infections

Infections

Some

Some infections

infections are

are caused

caused byby

own epithelial

own

epithelial flora-self

flora-self

contamination

contamination

Nasal

Nasal carriage

carriage most

most common

common

Hospitals

Hospitals

*Dirty

*Dirty hands,

hands, towels,

towels, and

and daycare

daycare

Airborne?????

Airborne?????

Community

Community

Predisposing

Predisposing Factors

Factors Of

Of

Susceptibility

Susceptibility

Integument

Integument injury

injury

Burns

Burns and

and trauma

trauma

Foreign

Foreign objects

objects

AA history

history of

of chronic

chronic Infections

Infections

Hormonal

Hormonal changes

changes and

and stress

stress

Immunocompromised

Immunocompromised

Clinical Manifestations

Clinical

Manifestations Of

Of

MRSA

MRSA

AA localized,

localized, superficial

superficial abscess

abscess

oror

Invasion

Invasion of

of lymphatics,

lymphatics, blood,

blood,

and major

and

major organs

organs

Superficial Infections

Superficial

Infections

Superficial Infections Superficial Infections

Scalded Skin

Scalded

Skin Syndrome:

Syndrome:

Classic TToxic

Classic

oxic Shock

Shock

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

www.aafp.org/afp/ 20000815/804.html

www.aafp.org/afp/

20000815/804.html

  • S. S. aureus

aureus Impetigo

Impetigo

www.med.sc.edu:85/ fox/staph- impetigo.jpg
www.med.sc.edu:85/ fox/staph-
impetigo.jpg

Systemic

Systemic SS aureus

aureus InIn the

the Lower

Lower

spine spine

..

SSystemic

ystemic Menstrual

Menstrual TToxic

oxic

Shock

Shock ByBy MRSA

MRSA

Most

Most major

major organs

organs fail

fail with

with

disseminated

disseminated MRSA

MRSA (TSS-1)

(TSS-1)

SS ystemic Menstrual TToxic Shock ByBy MRSA  Most Most major major organs organs fail fail

www.web.net/terrafemme/ cashnightmare.htm

How Accurate

How

Accurate Can

Can Your

Your

Diagnosis Of

Diagnosis

Of MRSA

MRSA Be?

Be?

How Accurate How Accurate Can Can Your Your Diagnosis Of Diagnosis Of MRSA MRSA Be? Be?

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

Biotechnology:

Biotechnology: Current

Current Drug

Drug

Treatments For

Treatments

For MRSA

MRSA

MRSA

MRSA Drugs

Drugs of

of Choice:

Choice:

Linezolid-Protein

Linezolid-Protein synthesis

synthesis inhibitor

inhibitor

Daptomycin-Causes membrane

Daptomycin-Causes

membrane

depolarization inin bacteria-so

depolarization

bacteria-so nono

membrane

membrane transport

transport

Vancomycin-A

Vancomycin-Acts

cts byby interfering

interfering

with the

with

the construction

construction of

of cell

cell wall.

wall.

Still works

Still

works well

well with

with other

other antibiotics

antibiotics

Alternatives:

Alternatives: Synercid,

Synercid, Rifampin

Rifampin

Third-Line

Third-Line agents:

agents: TMP-SMX

TMP-SMX (Sulfa)

(Sulfa)

Biotechnology:

Biotechnology: Drugs

Drugs InIn

Development

Development

Oritavancin-Binds

Oritavancin-Binds toto normal

normal cell

cell

wall

wall precursors

precursors

Tigecyclin-Works

Tigecyclin-Works onon efflux

efflux pumps

pumps

Dalbavancin-

Dalbavancin- Bacteriacidal

Bacteriacidal

Biotechnology: AA Novel

Biotechnology:

Novel Vaccination

Vaccination

For SS Aureus

For

Aureus

Development

Development of

of StaphVAX®,

StaphVAX®, aa

polysaccharide conjugate

polysaccharide

conjugate vaccine

vaccine

against

against S.

S. aureus

aureus infections

infections

The

The results

results of

of the

the phase

phase 33 clinical

clinical

trials of

trials

of the

the vaccine

vaccine (Staph

(Staph VAX)

VAX)

will bebe presented

will

presented 2006

2006 according

according

toto the

the NIH.

NIH.

Public Health

Public

Health Response

Response and

and CDC

CDC

TTechnical

echnical help

help for

for healthcare

healthcare professionals

professionals

National

National program

program of

of surveillance

surveillance

Evidence-based educational

Evidence-based

educational campaigns

campaigns

National

National resource

resource library

library

Researching

Researching S.

S. aureus

aureus toxins

toxins

More info?

More

info? GoGo toto www.cdc.goc

www.cdc.goc

(CDC,2005 (CDC,2005))

Prevention

Prevention

Draining

Draining infections

infections must

must bebe kept

kept covered

covered

TTalk

alk toto your

your physician

physician about

about wound

wound management

management

techniques

techniques

Wash hands

Wash

hands frequently

frequently with

with soap

soap and

and water

water

Avoid sharing

Avoid

sharing personal

personal items

items

Wipe objects

Wipe

objects down

down with

with alcohol.

alcohol.

Advise

Advise health

health care

care workers

workers toto wash

wash their

their hands

hands

before touching

before

touching you

you or

or your

your hospital

hospital equipment

equipment

The Real

The

Real Cost

Cost Of

Of Infectious

Infectious

Diseases

Diseases

The Real The Real Cost Cost Of Of Infectious Infectious Diseases Diseases

Rising

Rising Rates

Rates Of

Of Resistant

Resistant Bacterial

Bacterial

Infections=Rising Budget

Infections=Rising

Budget

Rising Rising Rates Rates Of Of Resistant Resistant Bacterial Bacterial Infections=Rising Budget Infections=Rising Budget

Summary

Summary

Multiple

Multiple MRSA

MRSA isolates

isolates are

are circulating

circulating inin

your local

your

local hospital

hospital and

and community

community

MRSA

MRSA has

has many

many mechanisms

mechanisms resistance

resistance

and virulence

and

virulence factors

factors

MecA

MecA gene

gene isis the

the gene

gene responsible

responsible for

for

methicillin resistance

methicillin

resistance

Many

Many of

of the

the MRSA

MRSA isolates

isolates are

are encoded

encoded

with the

with

the Sccmec

Sccmec mobile

mobile element

element inin them

them

MRSA

MRSA must

must bebe isolated

isolated and

and treated

treated

aggressively

aggressively toto prevent

prevent secondary

secondary

infections and

infections

and spread

spread

That’s All

That’s

All Folks!!

Folks!! Any

Any

Questions????

Questions????

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

References

References

11 Mitchell,

Mitchell, David.MRSA.”what’s

David.MRSA.whats New”.

New. Inoculum.

Inoculum. Volume

Volume 8,

8, number

number 22

(1999)

(1999) 1-12.

1-12.

22 textbookofbacteriology.net/resantimicrobial.html

textbookofbacteriology.net/resantimicrobial.html

33 healthsciences.columbia.edu/

healthsciences.columbia.edu/

dept/ps/2007/mid/2006/transcript_02_mid2222.pdf

dept/ps/2007/mid/2006/transcript_02_mid

.pdf

44 http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs

http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs

5. Foster,

5.

Foster, Timothy.

Timothy. The

The staphylococcus

staphylococcus aureus

aureus “superbug”.J.

“superbug”.J. clin

clin

Ivestigation

Ivestigation

Volume number114

Volume

number114 (2004)

(2004) 1693-1696.

1693-1696.

6. www.channing.harvard.edu/4a.htm

6.

www.channing.harvard.edu/4a.htm

7. ww.ncbi.nlm.nih.gov.

7.

ww.ncbi.nlm.nih.gov.

8. www.aafp.org/afp/

8.

www.aafp.org/afp/ 20000815/804.html

20000815/804.html

9. Journal

9.

Journal of

of Clinical

Clinical Microbiology

Microbiology,, June

June 2000,

2000, p.

p. 2378-2380,

2378-2380, Vol.

Vol. 38,

38, No.

No. 66

0095-1137/04.00+0

0095-1137/04.00+0

10.

10. www.FDA.com

www.FDA.com (FDA

(FDA archives)

archives)

11.www.postgradmed.com/issues/2001/10_01/hoel.htm

11.www.postgradmed.com/issues/2001/10_01/hoel.htm

  • 12. 12. www.cdc.gov/ncidod/hip/aresist/mrsa_CDCactions.htm

www.cdc.gov/ncidod/hip/aresist/mrsa_CDCactions.htm

13. www.medscape.com

13.

www.medscape.com

1414 http://www.nabi.com/images/factsheets/fsStaphVAX.pdf

http://www.nabi.com/images/factsheets/fsStaphVAX.pdf