deck 7 Flashcards
What bacterium is responsible for 90% of all bone infections?
Staph aureus
In the case, the infected compound bone fracture was cleaned and re-set. After 6 weeks one bone was not set correctly. Why?
edema from the initial breaksinflammation from infection, leading to more edema
How does osteomyelitis show on a radiograph? (radiopaque/radiolucent)
radiolucent where the normal bone opacity would be
What are the characteristics of staph?Gram?shape?oxygen utilization?motile?forms spores?
Gram + coccus about 1um in diameterfacultative aerobes/anaerobesnonmotilenonspore-former
What are the microbiology lab tests that distinguish staph aureus from other microbes?How are other staph different?
catalase + (distinguish from strep)coagulase + (other staph coagulase -)
What are the three types of hemolysis?
beta - complete lysis of blood agaralpha - blood agar turning green due to change in oxidation state of iron in blood (from hydrogen peroxide and acids)gamma - no lysis on blood agar plate
What microbe is responsible for: 500,000 cases of post-surgical infection annually100,000 cases of infectious endocarditis annually3K-35K cases of pneumonia (post-influenza)
staphylococcus aureus
What is the number 1 cause of blood stream infections?What is number 2?
1) staph epidermidis2) staph aureus
What diseases is staph aureus responsible for causing?
post-influenza pneumoniaendocarditisblood stream infectionsdeath in AIDs patientsUTIskin and soft tissue infections (boils)bone infections
Staph aureus has a 10 year cycle. What is this significant for?
New strains emerge every 10 years (except TSST-1 staph aureus broke the cycle)
Does staph aureus make toxins?What type of pathogen is it? Intra/extracellular?
It makes many cell surface and secreted toxinsIt is an extracellular pathogen with regard to PMNs and macrophages
What is staph aureus resistant to?
drying and some antibiotics
What are the cell surface virulence factors of staph aureus?(there are 5)
bound coagulase proteinfibronectin binding proteinscollagen binding proteinsvitronectin binding proteinsprotein A
What is bound coagulase protein? What is its purpose?
It is a cell surface virulence factor that converts fibrinogen to fibrin to surround the bacterium with self and to wall itself off
What is protein A? What is its purpose?
It is a cell surface virulence factor.It is a protein with 4 domains that bind the Fc portion of IgG and turn them backwards -> antiphagocytic
What are the secreted virulence factors of staph aureus?(there are 16)
free coagulase protein4 hemolysins: alpha, beta, gamma, deltahyaluronidasestaphylokinaselipaseDNasesRNasesproteasesbeta-lactamasesPBP2a for methicillin resistanceTSST-1staphylococcal enterotoxinsstaphylococcal exfoliative toxins A & B
What is free coagulase protein? What is its purpose?
It is a secreted virulence factor that activates the clotting cascade to presumably wall itself off
What is alpha hemolysin toxin? What is its purpose?
It is a secreted virulence factor and is a 30K protein that homo-heptamerizes to form a pore in membranes. It is dermonecrotic for human skin and blocks nerve repolarization. (only hemolytic in rabbits)
What is beta hemolysin toxin? What is its purpose?
It is a secreted virulence factor, is the hot:cold hemolysin, and is a sphingomyelinase
What is gamma hemolysin toxin? What is its purpose?
It is a secreted virulence factor, is hemolytic, and is a 2 component hemolysin. There are multiple copies of both parts that come together as hetero-heptamer pore formers.
What is delta hemolysin toxin? What is its purpose?
It is a secreted virulence factor and a small peptide that either acts as a surfactant to solubilize host cell membranes or is a small pore former
Staph aureus can have redundant toxinsT/F
yes. this makes determining each toxin’s role in disease difficult
What is hyaluronidase? What is its purpose?
It is a secreted virulence factor and spreading factor. It is an enzyme that cleaves hyaluronic acid in ground substance
What is staphylokinase? What is its purpose?
It is a secreted virulence factor and spreading factor. It breaks clots that have formed in walling off the organisms
What is lipase? What is its purpose?
It is a secreted virulence factor and an enzyme required for growth on the skin. Fatty acids in skin are toxic to bacteria and staphylococci have the ability to survive on the skin because of this
What is TSST-1? What receptors does it interact with? What is the result?
Toxic shock syndrome toxin-1Secreted superantigen that cross links MHC-II alpha chain to the variable part of the beta chain of the TCR, resulting in massive cytokines released from macrophages/T cells
What diseases is TSST-1 responsible for?
menstrual TSS1/2 of nonmenstrual staphylococcal TSS
What are staphylococcal enterotoxins? What types are there? What receptors do they bind?
A-E and I and SE-like G, H, J-KThey are superantigens likeTSST-1 except different Vbeta-TCRs stimulated; some have two MHC-II sites
What routes of administration of staphylococcal enterotoxins lead to what effects?
Oral - vomiting, diarrhea 2-8 hours after ingesting (no fever)IV or lungs - TSS
What are staphylococcal exfoliative toxins? What types are there? What disease is caused in what age? Why are others resistant?
A & BSerine proteases that specifically cleave desmoglein 1 (only found in neonatal epidermis), causing separation of layers of the skin -> scalded skin syndrome in neonatesolder individuals are resistant due to the dominance of desmoglein 3 in adult skin
T/FEvery staphyloccus aureus strain makes one of the cytolysins and one of the superantigens
True
Where are most virulence factors found in the bacterial genome?
mobile genetic elements: pathogenicity islands, bacteriophages, plasmids
T/FStaph aureus’ core chromosome is relatively nonvirulent.
True
What are the mechanisms of global regulation of secreted toxin production?
Histidine kinases in cell membrane sense oxygen and phosphorylate a response regulator (DNA binding protein). Octapeptides are produced, build up, and will activate Agr C. Then, it activates a response regulator to bind to DNA leading to RNA III production, which leads to delta toxin production and exotoxin transcription.
What is the relevance of having an oxygen sensing system as a global regulator?
Staph won’t make toxins until oxygen is present. This mechanism makes that happen. eg. menstrual TSS only happens with oxygen availability
How are the MRSA strains classified?
HA-MRSA / CA-MRSAalso by pulse field gel electrophoresisUSA300USA400USA200USA100
What DNA coding element is found on HA-MRSA? CA-MRSA?
HA-MRSA - SCCmec IICA-MRSA - SCCmec II or IV
What is present in the SCCmec DNA coding element?
The gene that encodes PBP2a, which leads to resistance
What are the highlights of the USA300 MRSA strain? Diseases it causes?
common on skin (lots of alpha toxin production & lipase)SCCmec IVcauses serious necrotizing pneumonia, usually in children, and soft tissue infections in all ages
What are the highlights of the USA400 MRSA strain?Diseases it causes?
SEB+ or SEC+SCCmecIVcauses serious necrotizing pneumonia and TSS usually in children (nonmenstrual)
What are the highlights of the USA200 MRSA strain? Diseases it causes?
TSST-1 +most common on mucosal surfacesSCCmec II or IVcauses serious necrotizing pneumonia and TSS in all ages; rarely causes skin infections
What are the highlights of the USA100 MRSA strain?
HA-MRSAcommon
What are the other Staph aureus virulence factors? These have less importance for virulence.Has vaccination against any of these been successful?
-capsules: small (more virulent) or large (less virulent)-slime (also called polysaccharide intercellular adhesion)-Iron-surface proteins (siderophores and related iron uptake systems)Vaccination has NOT been successful. The only vaccine candidates that have given complete protection are toxoids of exotoxins.
