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S. aureus Biofilms Staphylococcus aureus •ALL STAPHYLOCOCCI are: • 1. Gram-positive • 2. Cocci • 3. Clusters (Grape clusters) QuickTime™ and a Cinepak decompressor are needed to see this picture. QuickTime™ and a Cinepak decompressor are needed to see this picture. Levels of Infection • • • • Colonization Skin infections Metastatic Infections Toxinoses Colonization • Asymptomatic • The nares and throat of 3050% of normal healthy adults are colonized • Adhesins involved in colonization • This can result in spread of the infection to others • Autoinoculation QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. S. aureus infections • Skin infection. Can be caused by autoinoculation or spread from person-to-person (sometimes animal-to-person) • S. aureus is the most common cause of pyogenic skin infections – – – – – – Folliculitis Furuncle Carbuncle Impetigo Cellulitis Necrotizing Fasciitis Folliculitis • Superficial infection of the hair follicle • Self-limiting Furuncle • Deeper-seated than folliculitis • Pyogenic - abscess Carbuncle • Furuncles fused together Impetigo • Contagious • Usually on face • Bullous impetigo larger bullae, may be on body QuickTime™ and a TIFF(Uncompressed) decompressor are needed to see this pi cture. Cellulitis • Cellulitis is usually associated with Streptococcus • Can accompany foot ulcers in diabetic patients • Deep tissue infection • Subcutaneous or submucosal Necrotizing Fasciitis Infection of the superficial muscle fascia and adjacent subcutaneous tissue. More often caused by Group A Strep Metastatic S. aureus infections • Endocarditis • Pneumonia (nosocomial, CF-related, post-influenza) • Pyomyositis • Epidural abscess • Brain abscess • Osteomyelitis OSTEOMYELITIS QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. • Collagen binding protein S. aureus Toxinoses • Toxic shock syndrome • Scalded skin syndrome • Food poisoning Toxic Shock Syndrome • Associated with tampon use in early 80’s - ignored for a while but is re-emerging • Soccer shoes in England • Must be colonized with a TSST-producing strain and must lack antibodies • High fever, flushing, sloughing of skin on extremeties QuickTime™ and a TIFF(Uncompressed) decompressor are needed to see this pi cture. Qui ckTi me™ and a TIFF (Uncompressed) decompressor are needed to see this pictur e. Qui ckT ime™ and a T IFF (Uncompres sed) decompres sor are needed to s ee this picture. Staphylococcal superantigens QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Scalded Skin Syndrome • Usually in children and neonates • Erythema & sunburn-like rash • Desquamation due to exfoliatin toxin Food Poisoning • Food poisoning vs. food infection: staphylococcal enterotoxins (SEA, SEB etc.) • 2-6 hours between ingestion and symptoms • The toxin mainly induces vomiting • Staph is salt tolerant & can grow in foods that other bacteria can’t like ham Antibiotic resistance in S. aureus 1944 -lactamase 1940 Penicillin 1960 Methicillin/ Oxacillin 1970’s mecA 1996-VISA 2002 VanA Vancomycin 2000’s Daptomycin S. aureus: The “Superbug” QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. S. aureus Biofilms Diabetic foot ulcer Catheter Endocarditis QuickTime™ and a Cinepak decompressor are needed to see this picture. Jefferson et al. AAC 49(6); 2467 55 yo wm with Type II DM had severe osteoarthritis of the rt knee for years. 03/07 underwent rt total knee replacement. PostOp course uncomplicated. Did well until 5/07 when he developed increasing pain, swelling, and erythema of rt knee joint. Aspiration of knee joint revealed frank pus. Culture grew MSSA. Patient admitted and treated with IV vancomycin (penicillin allergy). ID consulted and recommended removal of joint hardware followed by prolonged IV vanc. Patient and family decided against joint removal and opted for debridment and prolonged antibiotics. The joint was irrigated and debrided. Patient received 6 wks IV vanc with rifampin followed by 2 mos PO bactrim. Joint improved without significant pain and patient was able to ambulate. 8-07 patients PC stopped bactrim. 5 days later, patient presented with increasing erythema, pain and swelling of the knee joint w/ fevers. Aspiration of the joint revealed frank pus and cultures grew MSSA. He was taken to the OR and all joint hardware was removed, an antibiotic spacer was placed, and he will receive an additional 6 wks vanc and rifampin before consideration of joint replacement. Inserted synthetic devices Polysaccharide intercellular adhesin PIA/PNAG What controls biofilm formation in S. aureus? O2 • External, environmental factors – Ethanol, NaCl, glucose • Internal regulators – IcaR, B, SarA NaCl EtOH Glucose B S SarA ? - icaR - icaA icaD icaB icaC icaR • Phase variation – IS elements IcaB Bioinformatics Approach • Different strains have different biofilm-forming capacities. • Can we predict biofilm formation based on sequence analysis?