Methicillin Resistant Methicillin Resistant Staphylococcus Staphylococcus AureusAureus

Barbara Jennings-SpringBarbara Jennings-Spring

Seminar in Molecular Biology 360Seminar in Molecular Biology 360

Smith CollegeSmith College

What Is MRSA?What Is MRSA?

MRSA is “Methicillin Resistant MRSA is “Methicillin Resistant Staphylococcus aureusStaphylococcus aureus

Is a bacteria that is resistant to a synthetic penicillin- methicillin. Is a bacteria that is resistant to a synthetic penicillin- methicillin.

MRSA causes a variety of disseminated, lethal infections in MRSA causes a variety of disseminated, lethal infections in humans.humans.

Has the ability to easily transfer resistant genes to other species Has the ability to easily transfer resistant genes to other species directly and indirectlydirectly and indirectly

Overuse of antibiotics imposes selective pressures which Overuse of antibiotics imposes selective pressures which mediates the acquisition of resistancemediates the acquisition of resistance

ObjectiveObjective

To gain a broader understanding of the resistance To gain a broader understanding of the resistance mechanisms and virulence factors involved with MRSA mechanisms and virulence factors involved with MRSA and how this disease impacts on a physical and global and how this disease impacts on a physical and global levellevel

Research Research

History of MRSAHistory of MRSA The basic Biology of The basic Biology of Staphylococcus aureusStaphylococcus aureus Molecular Basis For Virulence factors And Molecular Basis For Virulence factors And

ResistanceResistance Clinical Presentation Of DiseaseClinical Presentation Of Disease Detection Of pathogenDetection Of pathogen Biotechnology Treatments Biotechnology Treatments Public Health StrategiesPublic Health Strategies Political And Social Consequences Political And Social Consequences

A Timeline Of Antibiotic Resistance A Timeline Of Antibiotic Resistance

1941 1941 PenicillinPenicillin 1943 Streptomycin1943 Streptomycin 1945 Cephalosporins1945 Cephalosporins 1950 Tetracycline1950 Tetracycline 1952 Erythromycin1952 Erythromycin 1956 1956 VancomycinVancomycin

1960 1960 MethicillinMethicillin 1962 Lincomycin1962 Lincomycin 1962 Quinolones1962 Quinolones

1970 Penems1970 Penems

1980 Monobactams1980 Monobactams 2010 Could this be the end of an antibiotic era???2010 Could this be the end of an antibiotic era???

History Of History Of S aureusS aureus ResistanceResistance

The Basic Characteristics Of The Basic Characteristics Of S S aureusaureus

Gram positiveGram positive Non-motileNon-motile SphericalSpherical Grows in chainsGrows in chains Resembles clumps of grapesResembles clumps of grapes Golden colorGolden color Hemolytic pattern on blood agarHemolytic pattern on blood agar Produces coagulase and catalase enzymesProduces coagulase and catalase enzymes

img/staph_em.jpg

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

Mechanism Of ResistanceMechanism Of Resistance

http://www.jci.org/cgi/content/full/114/12/1693/F1http://www.jci.org/cgi/content/full/114/12/1693/F1

http://www.jci.org/cgi/content/full/114/12/1693/F1http://www.jci.org/cgi/content/full/114/12/1693/F1

Horizontal Gene Transfer-Another Horizontal Gene Transfer-Another Mechanism For ResistanceMechanism For Resistance

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

Summary of Virulence Summary of Virulence Determinants Of Determinants Of Staphylococcus Staphylococcus

aureusaureus

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

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

Virulence Factors: Avoiding Host DefensesVirulence Factors: Avoiding Host Defenses

Cell WallCell Wall

Cytoplasmic membrane- Osmotic barrier prevents Cytoplasmic membrane- Osmotic barrier prevents disequilibrium of ionic content. Pdisequilibrium of ionic content. Preventing cell reventing cell osmotic instability and susceptibility to lysis osmotic instability and susceptibility to lysis

Polysaccharide capsule-slime layer; adhesin. Inhibits Polysaccharide capsule-slime layer; adhesin. Inhibits phagocytosisphagocytosis

Petidoglycan-Allows bacteria to attach host’s cell Petidoglycan-Allows bacteria to attach host’s cell membranesmembranes

Protein A- Immunological disguise. Protein A- Immunological disguise.

Invasive enzymesInvasive enzymes

Coagulase Complex-Seals off infection, preventing Coagulase Complex-Seals off infection, preventing phagocytic engulfmentphagocytic engulfment

Protease, lipase, & DNase provide nourishment for Protease, lipase, & DNase provide nourishment for MRSA bacteriumMRSA bacterium

FAME-(Fatty acid modifying enzyme) modifies the anti-FAME-(Fatty acid modifying enzyme) modifies the anti-bacterial lipids side chain-inactivating antibiotic actionbacterial lipids side chain-inactivating antibiotic action

Staphylokinase-Fibrinolysisn aids the in spreading Staphylokinase-Fibrinolysisn aids the in spreading factorfactor

Hyaluronidase- Destroys connective tissueHyaluronidase- Destroys connective tissue

Damage To The Host: Extracellular Damage To The Host: Extracellular Products Products

Leukocidins-Kills White blood cells Leukocidins-Kills White blood cells (WBC’S)(WBC’S)

Alpha, Beta, Delta toxins-These Alpha, Beta, Delta toxins-These damaging toxins bid to to cell wall damaging toxins bid to to cell wall surface, forms a pore, and cellular surface, forms a pore, and cellular machinery of host cell leak out machinery of host cell leak out

Source Of MRSA InfectionsSource Of MRSA Infections

Some infections are caused by Some infections are caused by own epithelial flora-self own epithelial flora-self contaminationcontamination

Nasal carriage most commonNasal carriage most common HospitalsHospitals *Dirty hands, towels, and daycare*Dirty hands, towels, and daycare Airborne?????Airborne????? CommunityCommunity

Predisposing Factors Of Predisposing Factors Of SusceptibilitySusceptibility

Integument injuryIntegument injury Burns and traumaBurns and trauma Foreign objectsForeign objects A history of chronic InfectionsA history of chronic Infections Hormonal changes and stressHormonal changes and stress Immunocompromised Immunocompromised

Clinical Manifestations Of Clinical Manifestations Of MRSAMRSA

A localized, superficial abscess A localized, superficial abscess or or

Invasion of lymphatics, blood, Invasion of lymphatics, blood, and major organsand major organs

Superficial InfectionsSuperficial Infections

Scalded Skin Syndrome: Scalded Skin Syndrome: Classic Toxic ShockClassic Toxic Shock

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

S. aureusS. aureus Impetigo Impetigo

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

impetigo.jpg

Systemic Systemic S aureusS aureus In the Lower In the Lower spinespine

..

SSystemic Menstrual Toxic ystemic Menstrual Toxic Shock By MRSAShock By MRSA

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

www.web.net/terrafemme/ cashnightmare.htm

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

Accuracy of medium in discriminating S. aureus and

CoNS

Identification method

S. aureus (n = 114)

CoNS (n = 22)

Sensitivity (%) Specificity (%)

CHROMagar Staph aureus

100 0a 100 100

DNase 98.0 4.6 98.0 95.4

MSA 98.0 36.5 98.0 63.5

Coagulaseb 100 0 100 100

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 Biotechnology: Current Drug Treatments For MRSATreatments For MRSA

MRSA Drugs of Choice:  MRSA Drugs of Choice:  Linezolid-Protein synthesis inhibitor Linezolid-Protein synthesis inhibitor

Daptomycin-Causes membrane Daptomycin-Causes membrane depolarization in bacteria-so no depolarization in bacteria-so no membrane transportmembrane transport

Vancomycin-AVancomycin-Acts by interfering cts by interfering with the construction ofwith the construction of cell wall. cell wall. Still works well with other antibioticsStill works well with other antibiotics

Alternatives:  Alternatives:  Synercid, RifampinSynercid, Rifampin Third-Line agents:  Third-Line agents:  TMP-SMX (Sulfa)TMP-SMX (Sulfa)

Biotechnology: Drugs In Biotechnology: Drugs In DevelopmentDevelopment

Oritavancin-Binds to Oritavancin-Binds to normalnormal cell cell wall precursorswall precursors

Tigecyclin-Works on efflux Tigecyclin-Works on efflux pumpspumps

Dalbavancin- BacteriacidalDalbavancin- Bacteriacidal

Biotechnology: A Novel Biotechnology: A Novel Vaccination For Vaccination For S AureusS Aureus

Development of StaphVAX®, a Development of StaphVAX®, a polysaccharide conjugate polysaccharide conjugate vaccine against vaccine against S. aureusS. aureus infections infections

The results of the phase 3 clinical The results of the phase 3 clinical trials of the vaccine (Staph VAX) trials of the vaccine (Staph VAX) will be presented 2006 according will be presented 2006 according to the NIH. to the NIH.

Public Health Response and CDCPublic Health Response and CDC

Technical help for healthcare professionalsTechnical help for healthcare professionals

National program of surveillanceNational program of surveillance

Evidence-based educational campaignsEvidence-based educational campaigns

National resource libraryNational resource library

Researching Researching S. aureusS. aureus toxins toxins

More info? Go to www.cdc.goc More info? Go to www.cdc.goc (CDC,2005(CDC,2005))

PreventionPrevention

Draining infections must be kept coveredDraining infections must be kept covered

Talk to your physician about wound management Talk to your physician about wound management techniquestechniques

Wash hands frequently with soap and waterWash hands frequently with soap and water

Avoid sharing personal itemsAvoid sharing personal items

Wipe objects down with alcohol.Wipe objects down with alcohol.

Advise health care workers to wash their hands Advise health care workers to wash their hands before touching you or your hospital equipmentbefore touching you or your hospital equipment

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

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

SummarySummary

Multiple MRSA isolates are circulating Multiple MRSA isolates are circulating in your local hospital and communityin your local hospital and community

MRSA has many mechanisms MRSA has many mechanisms resistance and virulence factorsresistance and virulence factors

MecA gene is the gene responsible for MecA gene is the gene responsible for methicillin resistancemethicillin resistance

Many of the MRSA isolates are encoded Many of the MRSA isolates are encoded with the Sccmec mobile element in with the Sccmec mobile element in themthem

MRSA must be isolated and treated MRSA must be isolated and treated aggressively to prevent secondary aggressively to prevent secondary infections and spreadinfections and spread

That’s All Folks!! Any That’s All Folks!! Any Questions????Questions????

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

ReferencesReferences

1 Mitchell, David.MRSA.”what’s New”. Inoculum. Volume 8, number 2 1 Mitchell, David.MRSA.”what’s New”. Inoculum. Volume 8, number 2 (1999) 1-12.(1999) 1-12.

2 textbookofbacteriology.net/resantimicrobial.html2 textbookofbacteriology.net/resantimicrobial.html 3 healthsciences.columbia.edu/ 3 healthsciences.columbia.edu/

dept/ps/2007/mid/2006/transcript_02_middept/ps/2007/mid/2006/transcript_02_mid2222.pdf .pdf 4 http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs4 http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs 5. Foster, Timothy. The 5. Foster, Timothy. The staphylococcus aureusstaphylococcus aureus “superbug”.J. clin “superbug”.J. clin

IvestigationIvestigation Volume number114 (2004) 1693-1696.Volume number114 (2004) 1693-1696. 6. www.channing.harvard.edu/4a.htm6. www.channing.harvard.edu/4a.htm 7. ww.ncbi.nlm.nih.gov.7. ww.ncbi.nlm.nih.gov. 8. www.aafp.org/afp/ 20000815/804.html8. www.aafp.org/afp/ 20000815/804.html 9. 9. Journal of Clinical MicrobiologyJournal of Clinical Microbiology, June 2000, p. 2378-2380, Vol. 38, No. 6, June 2000, p. 2378-2380, Vol. 38, No. 6

0095-1137/04.00+00095-1137/04.00+0 10. www.FDA.com (FDA archives)10. www.FDA.com (FDA archives) 11.www.postgradmed.com/issues/2001/10_01/hoel.htm11.www.postgradmed.com/issues/2001/10_01/hoel.htm

12. 12. www.cdc.gov/ncidod/hip/aresist/mrsa_CDCactions.htmwww.cdc.gov/ncidod/hip/aresist/mrsa_CDCactions.htm 13. 13. www.medscape.comwww.medscape.com 14 http://www.nabi.com/images/factsheets/fsStaphVAX.pdf14 http://www.nabi.com/images/factsheets/fsStaphVAX.pdf