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Staphylococcus epidermidis:

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Staphylococcus epidermidis:

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    1. Staphylococcus epidermidis: Dr. Michelle Alfa Ph.D, FCCM Diagnostic Services of Manitoba St. Boniface General Hospital Site

    2. Will the REAL S.epidermidis please stand up??

    3. Overview: Characteristics of Staphylococcus - Diseases Caused by S.epidermidis - Virulence Factors: Host infection In vivo versus environmental factors - invasive disease - biofilm formation on indwelling devices Unique virulence factors Prevention of infection

    4. Gram positive cocci in clusters - Catalase (+) Genus Staphylococcus has 37 species human infections: S.aureus, S.epidermidis, S.lugdenensis, S.saprophyticus Skin (axilla, head, nares) main reservoir (103 cfu/cm2) - S.aureus colonizes ~20% of people - S.epidermidis colonizes ~100% of people Classified by coagulase (+) vs (-) Multi-resistant to antibiotics Staphylococcus species: Characteristics

    5. S.epidermidis - Human infections

    7. Pathogenesis: Exposure: - Skin: reservoir - Trauma: e.g. surgery, line etc Localization: Biofilm: - adherance to catheter, implant - replication? biofilm formation; Dissemination/Damage: - shedding from biofilm - septicemia, inflammation

    8. Protective exopolymers:(aka; slime!) PNAG (poly-N-acetylglucosamine); protects form IgG, AMPs, phagocytosis and complement; synthesized from ica operon - 85% of device-related strains had gene vs 6% sapro strains (McCann et al 2008) (PGA(poly-gama-glutamic acid); protects from AMPs (anti-microbial peptides found on skin), & phagocytosis Toxins: PSMs: pro-inflammatory cytolysins (not strong) Staphyloferrins: siderophore iron acquisition Virulence Factors: S.epidermidis

    9. S.epidermidis Cell surface: Proteins & Polysaccharide

    10. Quorum Sensing: regulates biofilm formation - agr (accessory gene regulator); - luxS (AI-2; intraspecies communication); affects PNAG production (Note: this system found in many orgs) MSCRAMMs: (microbial surface components recognizing adhesive matrix molecules) Initial attachment phase - surface proteins on S.epidermidis (SdrF, SdrG etc) that bind to host matrix: collagen, fibronectin, fibrinogen, vitronectin Aggregation/biofilm maturation: - Surface proteins; Bap(biofilm associated protein) & Aap (accumulation associated protein) - Exopolymer PNAG (also called PIA); intercellular adhesion Virulence Factors: S.epidermidis

    11. Quorum Sensing Systems: agr and LuxS

    12. S.epidermidis surface protein SdrF binds collagen

    13. Biofilm: S.epidermidis

    14. S. epidermidis: Biofilm protection from Host defenses Enters “non-aggressive” state reduced inflammation & chemotaxis of immune cells

    15. S.epidermidis Biofilm Composition:Polysaccharide & Protein (stronger than protein alone) Quorum sensing: “…organisms in the biofilm as a whole behave as a multicellular organism, able to resist treatment which would kill isolated cells.” (D. Mack et al 2007)

    16. Antibiotic Treatment Stimulators of biofilm? - Subinhibitory conc of Vanco stimulates biofilm (Cargill & Upton 2009) Therapeutic efficacy? - McCann et al 2008 Resistance development? - transfer of genes

    17. S.epidermidis: Antibiotic Resistance

    18. Treatment: Infection of Indwelling device Antibiotics: choice limited, long duration Usually requires removal of device

    19. Treatment: Novel methods Agr pheromones are species specific: Use synthetic peptides from one org to treat another org e.g. RIP (heptapeptide): is an RNAIII-inhibiting peptide: useful adjunct with antibiotics to inhibit agr-activation in S.aureus & S.epidermidis (Mack et al 2007)

    20. Prevention: Vaccinate against: PNAG, techoic acid, protein adhesins of org Short hospital stays to lessen risk of acquiring pathogenic nosocomial strains Remove foreign material (e.g. lines) as quickly as possible; reduce risk of line associated infection

    21. Ubiquitous skin distribution; normal flora Multi-resistant to wide range of antibiotics Most common cause of infections associated with indwelling devices Biofilm: key virulence factor? behaves like a multicellular organism - antibiotics ineffective against biofilm orgs - sheds organisms that seed other sites To cure infection? must remove device Unique Aspects of Pathogenesis:

    22. Summary: S.epidermidis: skin is reservoir (i.e endogenous) Opportunistic pathogen; Most common cause of device associated infections - traumatic bypassing of skin - indwelling device colonization? biofilm - shedding from device to spread systemically QS systems (agr, luxS); two-component response regulator systems control ? communication to form and maintain biofilm MSCRAMMs; exopolysaccharides & surface proteins - facilitate initiation and maturation of biofilm formed of both protein (SdrF etc) and polysaccharide (PNAG, PGA)

    23. References: Otto M Staphylococcus epidermidis – the “accidental” pathogen. Nature Reviews Microbiology 2009;7:555-567 Mack D, AP Davies, LG Harris, et al Microbial interactions in Staphylococcus epidermidis biofilms Anal Bioanal Chem 2007;387:399-408 McCann MT, BF Gilmore, SP Gorman Staphylococcus epidermidis device-related infections: pathogenesis and clinical management. J Pharm Pharmocol 2008;60:1551-1571 Anselmino M, M Vinci, C Comoglio et al Bacteriology of infected extracted pacemaker and ICD leads J Cardiovasc Med 2009;10:693-698 Uckay I, D Pittet, P Vaudaux et al Foreign body infections due to Staphylococcus epidermidis Annals of Med 2009;41:109-119 Arrecubieta C, M0H Lee, A Macey et al SdrF, a Staphylococcus epidermidis surface protein, binds Type I collagen. J Biol Chem 2007;282:18767-19776. Manual of Clinical Microbiology 9th Edition, P Murray, E Baron, J Jorgensen, M Landry, M Pfaller Editors, ASM publisher. Soderquist B, M Andersson, M Nilsson et al Staphylococcus epidermidis surface protei I (SesI) a marker of invasive capacity of S.epidermidis? J Med Microbiol Papers 2009 (doi:10.1099/jmm.0.008771-0) Cargil JS, M Upton Low concentrations of vancomycin stimulates biofilm formation in some clinical isolates of Staphylococcus epidermidis. Vadyvaloo V, Otto M Molecular genetics of Staphylococcus epidermidis biofilms on indwelling medial devices. Int J Artif Organs 2005;28:1069-1078. Visai L, Arciolo CR, Pietrocola G et al Staphylococcus biofilm components as targets of vaccines and drugs. Int J Artif Organs 2007;9:813-819 Jarlov JO Phenotypic characteristics of coagulase-negative staphylococci: typing and antibiotic susceptibility. APMIS suppl 1999;91:1-42. Speziale P, Visai L, Rindi S et al Prevention and treatment of Staphylococcus biofilms. Curr Med Chem 2008;30:3185-3195.

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