Staphylococcus Aureus Flashcards
general characteristics of Staphylococci?
-Gram + cocci, usually arranged as grape like clusters
-facultative anaerobes- can survive in high concentrations of NaCl, high lipid concentrations
- produce catalase- enzyme that converts hydrogen peroxide to water and oxygen (measure enzyme to determine it from strep)
- ubiquitous- commonly found on skin and mucous membranes of humans
- prolonged survival of inanimate objects under various condition, thick peptidoglycan layer
- causes opportunistic infections and a wide range of life threatening systemic diseases (skin, soft tissue, bones, urinary tracts)
What is the most virulent staphylococci genus?
S. Aureus -methicillin resistant S. Aureus (MRSA) known for causing serious infections in hospitalized patients and in previously healthy children and adults
-methicillin sensitive strains are referred to as MSSA
Unique lab characteristics of S. Aureus?
- colonies on plate turn yellow and, beta hemolytic on blood agar
- produces coagulase, an enzyme that converts fibrinogen to fibrin-> forms clot when mixed with plasma
- coagulase test- lysis of RBC, clearing colonies
- protein A inhibits antibody mediated clearance by binding Fc portion of IgG1, IgG2, IgG4 (complement cannot bind)
Epidemiology of S. Aureus?
- ubiquitous- humans are a major reservoir
- health care workers are carriers
- susceptible to high temperatures and disinfectants -can survive on objects
- hospital acquired MRSA- spread from health care workers, surgery, antibiotics, weakened immunity
- community acquired MRSA- cutaneous infection, sever pneumonia, being athlete, shaving, tattoos, gym equipment
Mr. B, a pastry chef, cuts his arm. Over the next week, noticed swelling at the site. After 4 days, initial site was larger and he developed a fever with chills. When he came to the emergency room, he had severe low back pain. He had an abscess over his arm. Pressure in lower spine. High WBC count. Gram stain showed gram + cocci in clusters. What happened?
- when he cut his arm, he made himself more susceptible to infection (skin infection)
- got into blood stream and affected his vertebrae, suggesting osteomyelitis
- organism is resistant to penicillin (make beta lactamase) but sensitive to nafcillin
-customers also developed severe vomiting and diarrhea (food poisoning)
- cultures show enterotoxin A
- S. Aureus causes greater variation of diseases
- skin infection, osteomyelitis, food poisoning
Why does S. Aureus cause more varied diseases than any other pathogen?
- high degree of genetic diversity
- ability to cause infection can vary based on production of virulence factors and how expressed
- overlapping functions of virulence factors
- superantigens
- has a capsule with exotoxins
How does S. Aureus cause diseases?
- direct invasion and destruction of tissue
- production of toxins, infection and intoxication
General pathogenesis of S. Aureus?
- pyogenic (pus) disease, abscess formation at local or metastatic sites
- immune response- intense, PMN with influx of macrophages and fibroblasts
- immune response will contain infection or it can spread to adjoining tissue or blood
- patients with congenital defects in chemotactic or phagocytic response are more susceptible to staph
- toxigenic disease- may or may not involve viable bacteria
Colonization of skin and mucus membranes mediated by ______. Encounter?
MSCRAMMs that allow them to bind to tissue
- live on people, fomites
- FnbpA, FnbpB
- CNAs (collagen adhesin)- mediates binding to collagen in connective tissue
- clumping factors A and B
Spread and transmission?
- direct contact with carrier or aerosols associated with respiratory infections
- facilitated by people more prone to be colonized or carriers (hospital workers, diabetics, IV drug users)
metastatic infections?
- usually requires implantation and previous damage to tissues, less bacteria when you stab yourself with something
- abscess in bones (osteomyelitis), joints, lungs, kidneys
- spread facilitated by elaboration of serine proteases, hyaluronidases, ligases, DNases (spread factors so they are not walled in)
Host response to infection?
- primary response is recruitment of PMNs
- anti-capsular and anti-MSCRAMM facilitate opsonization and protect against infection
Evasion of host response?
- anti phagocytic capsule
- protein A- binds Fc portion of IgG, prevents opsonophagocytosis of PMNs, prevents classical path of complement
- coagulase- fibrin clots protects bugs from WBC
- intracellular survival of small colony variants in endothelial cells and macrophages
- cytolytic exotoxins (panton valentine leukocidin P-V)
- P-V is linked with severe pulmonary and cutaneous infections
Toxins that mediate disease?
-if purified, they cause disease by themselves
Exfoliative Toxins (ETA, ETB)
- exfoliates skin
- superantigens- cytokine storm
- mediates staph scalded skin syndrome (SSSS)
- serine protease that splits desmoglein-1
Enterotoxins (A-X)
- superantigens
- stable to heating to 100 C for 30 mins and resistant to hydrolysis by gastric juices and jejunal enzymes
- Enterotoxin A most common associated with food poisoning
- Entero B and C associated with 50% non menstruation associated TSS
Toxic Shock Syndrome Toxin (TSST-1)
- superantigen
- strains that carry gene responsible 90% of menstruation associated TSS, 50% other cases
- can penetrate mucosal barriers
Clinical manifestations of S. Aureus?
-folliculitis- pyogenic infection in hair follicle, stye if in base of eyelid
-carbuncle- multiple interconnected boils that extend into deeper tissues, fever and chills point to systemic spread
-furuncle- extension of folliculitis, large, painful, underlying dead and necrotic tissue (abscess)
Antibiotic resistance factors?
beta lactamase:
- hydrolyzes classical penicillin
- plasmid encoded
- most Penicillin binding protein 2a (PBP2a):
- transpeptidase with alteration in binding site that results in reduced affinity for penicillin and cephalosporin class antibiotics -keeps cross linking peptidoglycan
- PBP2a encoded on different cassettes on staph chromosome (SCCmec)
- S. Aureus strains that express PBP2a referred to as MRSA strains (hospital or community)
Genetics of MRSA resistance?
mecA encodes for PBP2a on a pathogenicity island with other exotoxin genes:
- staph cassette chromosome (SCCmec)
- 11 different cassettes
hospital acquired (SCCmec types I and III):
- resistant to large number of antibiotics
- very large
- more genes, encodes more resistance
community acquired (Type IV SCC mecA)
- smaller, more susceptible to antibiotic
- resistant to meth and other beta lactams
Virulence factors of S. Aureus?
- possesses a polysaccharide capsule
- has a plethora of redundant cell surface and exotoxin virulence factors
