S. aureus S. aureus BiofilmsBiofilms

Staphylococcus aureusStaphylococcus aureus

•ALL STAPHYLOCOCCI are:ALL STAPHYLOCOCCI are:• 1. Gram-positive1. Gram-positive• 2. Cocci 2. Cocci • 3. Clusters (Grape clusters)3. Clusters (Grape clusters)

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Levels of InfectionLevels of Infection

• ColonizationColonization

• Skin infectionsSkin infections

• Metastatic InfectionsMetastatic Infections

• ToxinosesToxinoses

ColonizationColonization

• AsymptomaticAsymptomatic• The nares and throat of 30-The nares and throat of 30-

50% of normal healthy 50% of normal healthy adults are colonizedadults are colonized

• Adhesins involved in Adhesins involved in colonizationcolonization

• This can result in spread of This can result in spread of the infection to othersthe infection to others

• Autoinoculation Autoinoculation

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S. aureusS. aureus infections infections

• Skin infection. Can be caused by autoinoculation Skin infection. Can be caused by autoinoculation or spread from person-to-person (sometimes or spread from person-to-person (sometimes animal-to-person)animal-to-person)

• S. aureusS. aureus is the most common cause of pyogenic is the most common cause of pyogenic skin infectionsskin infections– FolliculitisFolliculitis– FuruncleFuruncle– CarbuncleCarbuncle– ImpetigoImpetigo– CellulitisCellulitis– Necrotizing FasciitisNecrotizing Fasciitis

FolliculitisFolliculitis

• Superficial Superficial infection of the infection of the hair folliclehair follicle

• Self-limitingSelf-limiting

FuruncleFuruncle

• Deeper-seated than Deeper-seated than folliculitisfolliculitis

• Pyogenic - abscessPyogenic - abscess

CarbuncleCarbuncle

• Furuncles fused together

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ImpetigoImpetigo

• ContagiousContagious

• Usually on faceUsually on face

• Bullous impetigo - Bullous impetigo - larger bullae, may be larger bullae, may be on body on body

Cellulitis Cellulitis

• Cellulitis is usually Cellulitis is usually associated with associated with StreptococcusStreptococcus

• Can accompany foot Can accompany foot ulcers in diabetic ulcers in diabetic patientspatients

• Deep tissue infectionDeep tissue infection• Subcutaneous or Subcutaneous or

submucosalsubmucosal

Necrotizing FasciitisNecrotizing Fasciitis

Infection of the Infection of the superficial muscle superficial muscle fascia and adjacent fascia and adjacent subcutaneous tissue.subcutaneous tissue.

More often caused by More often caused by Group A StrepGroup A Strep

Metastatic Metastatic S. aureusS. aureus infections infections

• EndocarditisEndocarditis

• Pneumonia (nosocomial, CF-related, Pneumonia (nosocomial, CF-related, post-influenza)post-influenza)

• PyomyositisPyomyositis

• Epidural abscessEpidural abscess

• Brain abscessBrain abscess

• OsteomyelitisOsteomyelitis

OSTEOMYELITISOSTEOMYELITIS

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• Collagen Collagen binding binding proteinprotein

S. aureusS. aureus Toxinoses Toxinoses

• Toxic shock syndromeToxic shock syndrome

• Scalded skin syndromeScalded skin syndrome

• Food poisoningFood poisoning

Toxic Shock SyndromeToxic Shock Syndrome

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• Associated with tampon use Associated with tampon use in early 80’s - ignored for a in early 80’s - ignored for a while but is re-emergingwhile but is re-emerging

• Soccer shoes in EnglandSoccer shoes in England• Must be colonized with a Must be colonized with a

TSST-producing strain and TSST-producing strain and must lack antibodiesmust lack antibodies

• High fever, flushing, High fever, flushing, sloughing of skin on sloughing of skin on extremetiesextremeties

Staphylococcal superantigensStaphylococcal superantigens

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Scalded Skin SyndromeScalded Skin Syndrome

• Usually in children Usually in children and neonatesand neonates

• Erythema & Erythema & sunburn-like rashsunburn-like rash

• Desquamation due Desquamation due to exfoliatin toxin to exfoliatin toxin

Food PoisoningFood Poisoning

• Food poisoning vs. food infection: Food poisoning vs. food infection:

staphylococcal enterotoxins (SEA, SEB etc.)staphylococcal enterotoxins (SEA, SEB etc.)

• 2-6 hours between ingestion and symptoms2-6 hours between ingestion and symptoms

• The toxin mainly induces vomitingThe toxin mainly induces vomiting

• Staph is salt tolerant & can grow in foods Staph is salt tolerant & can grow in foods

that other bacteria can’t like hamthat other bacteria can’t like ham

Antibiotic resistance in Antibiotic resistance in S. aureusS. aureus

1940Penicillin

1944-lactamase

1960Methicillin/Oxacillin

1970’smecA

Vancomycin

1996-VISA2002VanA

2000’sDaptomycin

S. aureusS. aureus: The “Superbug”: The “Superbug”

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S. aureusS. aureus Biofilms Biofilms

Diabetic foot ulcerDiabetic foot ulcer

EndocarditisEndocarditis

CatheterCatheter

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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 devicesInserted synthetic devices

Polysaccharide Polysaccharide intercellular adhesinintercellular adhesinPIA/PNAG PIA/PNAG

What controls biofilm formation in What controls biofilm formation in S. aureusS. aureus??

NaCl

EtOHGlucose• External, External,

environmental environmental factorsfactors– Ethanol, NaCl, Ethanol, NaCl,

glucoseglucose

• Internal Internal regulatorsregulators– IcaR, IcaR, BB, SarA, SarA

• Phase variationPhase variation– IS elementsIS elements

icaCicaBicaAicaR

B

SarA

icaR

-

-

IcaA

icaD

DIcaC

IcaB

?

O2

S

Bioinformatics ApproachBioinformatics Approach

• Different strains have different Different strains have different biofilm-forming capacities.biofilm-forming capacities.

• Can we predict biofilm formation Can we predict biofilm formation based on sequence analysis?based on sequence analysis?