Lecture 9 Flashcards
how is staphylococcus divided?
into pathogens and non pathogens based on possession of the enzyme coagulase
what are some traits of coagulase +?
are usually S. aureus and are pathogenic
what are some traits of coagulase - ?
are organisms like S.epidermidis and are less invasive
what are some general characteristics of Staphylococci?
- extracellular pathogen
- spherical cells arranged in irregular clusters
- gram positive
- lack spores and flagella
- common inhabitants of the skin and mucous membranes
What are some traits of S. aureus?
- grows in large round colonies grape like
- golden yellow colonies on blood agar plate
- withstands high salt, extremes in pH, and high temperatures
what trait does both S. aureus and Y. pestis share?
both are facultative anaerobes
what are the 2 groups S. aureus diseases are studied under?
infections and intoxications
what are infections?
the disease is caused by the bacteria themselves
what are intoxications?
disease is caused by the bacterial exotoxins, produced in the infected host or preformed in vitro
what are the mechanisms of pathogenesis for infections?
- bacteria gain access to damaged skin, mucosal or tissue site
- colonize by adhering to cells or extracellular matrix
- evade the host defense mechanisms and multiply
- cause tissue damage
what are some traits of local infections?
- usually remain localized at the portal of entry by the normal host defenses
- infection of skin and soft tissue is common
- common bacterial portals are hair follicles and breaks in skin
- foreign bodies like sutures and catheters are readily colonized
what are some traits of systemic infections?
- osteomyelitis
- bacteremia
- endocarditis
- pneumonia and empyema
what is osteomyelitis?
s. aureus invasion of the bone
what is bacteremia?
bacteria in the blood
what is endocarditis?
attacks the lining of the heart
what is pneumonia?
invading the lungs, inflammation of lungs, fluid fills within alveoli and bronchioles
what is empyema?
refers to the collection of pus in the space between the lung and the inner surface of the chest wall
what are some types of intoxications from staphylococcus?
- food intoxication
- staphylococcal scalded skin syndrome
- toxic shock syndrome
what is food intoxication?
ingestion of heat stable enterotoxins, GI distress
what is staphylococcal scalded skin syndrome?
toxin induces bright red flush, blisters, then peeling of the skin, danger comes from secondary bacterial infection
what is toxic shock syndrome?
toxemia leading to shock and organ failure
what are some epidemiology and pathogenesis traits?
- present in most environments
- readily isolated from fomite
- predisposition factors
- community acquired MRSA
what are some of the pre dispositions to infection?
- poor hygiene
- poor nutrition
- tissue injury
- preexisting primary infection
- diabetes
- immunodeficiency
what are the cell associated factors for virulence of Staph?
cell associated polymers and cell surface proteins
what are traits of cell associated polymers?
- cell wall polysaccharide
- teichoic acid (in peptidoglycan layer of gram positive)
- capsular polysaccharide
what are the traits of cell surface proteins?
protein A and clumping factor (bound coagulase)
how does Staph protect itself from phagocytosis?
- protein A
- bound coagulase
- capsule
what does protein A do?
it is a type 1 membrane protein that binds to IgG molecules on their heavy chain in Fc region to render them ineffective
what are some traits of Coagulase?
- can be bound to the outer surface of the bacteria or cell free
- converts fibrinogen into insoluble fibrin which causes clotting
- highly correlated with virulence
what is important about cell bound coagulase?
could provide an antigenic disguise if it clots fibrin on the cell surface
what is special about a staphylococcal lesion encased in fibrin?
could make the bacterial cells resistant to phagocytes, tissue bactericides, or even drugs which might be unable to diffuse to their bacterial target
what are the extracellular virulence factors?
enzymes and toxins
be able to identify some of the enzymes for virulence!
- free coagulase
- catalase
- lipase
- hyaluronidase
- DNAase
- thermonuclease
- staphylokinase
- phosphatase
what does hyaluronidase do?
- breaks down hyaluronic acid (component in proteoglycans, major component of the matrix between cells)
- enables bacteria to spread between cells throughout the body
what does staphylokinase do?
dissolves fibrin threads in blood clots, allowing S. aureus to free itself from clots, helps bacteria spread to new locations
what do Lipases do?
hydrolyze lipids, may help bacteria survive in sebaceous glands in the skin. May aid in development of skin infections and subcutaneous infections
what does DNAase do?
marker for virulence that digests DNA
what does penicillinase do?
inactivates penicillin, doesn’t directly influence virulence but influences treatment options
what are the toxins used for virulence?
- hemolysins
- leukocidin
- enterotoxins
- exfoliative toxin
- toxic shock syndrome toxin
what are some traits to alpha hemolysin?
- membrane toxin
- platelets and monocytes are sensitive to alpha toxin
- mode of action is likely by osmotic lysis
how does alpha hemolysin work?
- binds to the membranes of susceptible cells in a monomeric form
- subunits then oligmerize to form heptameric rings with central pore through which cellular contents leak
what does B toxin do?
its a sphingomyelinase which damages membranes rich in this lipid
the majority of human isolates of S. aureus dont express which type of hemolysin toxin?
beta
what does delta toxin do?
a very small peptide toxin produced by most strains of S. aureus that lyse Red blood cells
what do all hemolysin toxins do?
they lyse red blood cells
what are some traits of leukocidin?
- multicomponent protein toxin produced as separate components which act together to damage membranes
- hemolytic but less than alpha hemolysin
- 2% of S. aureus express it but nearly 90% of the strains isolated from dermonecrotic lesions express it
Leukocidin forms a hetero oligomeric transmembrane pore composed of what?
4 LukF and 4LukS subunits, forming an octameric pore in the affected membrane
generally what do leukocidins do?
lyse neutrophils and macrophages
what do enterotoxins do?
- they stimulate muscle contractions, nausea, and intense vomiting associated with food poisoning.
- when expressed systemically, can cause toxic shock syndrome
which toxin is heat stable, remaining active at 100 degrees celsius for 30 minutes?
enterotoxin
which toxins have superantigen activity?
- enterotoxins, they stimulate T cells non specifically without normal anitgenic recognition
- toxic shock syndrome toxin
what are the 6 antigenic types of enterotoxin?
- SE-A
- B
- C
- D
- E
- G
what is special about enterotoxins B and C?
cause 50% of non menstrual cases of TSS
what are some traits of toxic shock syndrome toxin?
- superantigen
2. non specific binding of toxin to receptors triggers excessive immune response
what are the properties skin has to prevent S. aureus colonization?
- low temperature
- low pH
- skin commensals
- antimicrobial peptides
what do keratinocytes do?
they produce keratin and express recognition receptors such as TLR2 and NOD2
what does TLR2 do?
recognizes S.aureus lipopeptides and lipotechoic acid
what does NOD2 do?
recognizes S. aureus peptidoglycan breakdown product muramyl-peptide
what does TLR2 and NOD2 signaling lead to?
activation of NF-kB and other transcription factors that induce transcription of pro-inflammatory mediators
what does S. aureus infection of skin result in?
- production of IL-1a, IL-1b, and IL-17
- induce keratinocyte production of anitmicrobial peptides
- granulopoiesis factors that promote neutrophil recruitment
what is PBP2a?
a penicillin binding protein that is intrinsically insensitive to methicillin and all beta lactams
