Lecture 9 Staph Aureus I

Question 1

What are the clinically relevant staphylococci?

Answer 1

Staphylococcus aureus
Staphylococcus epidermidis
Staphyococcus saprophyticus

Question 2

What are the general characterisitcs of staphylococci?

Answer 2

They are non-motile
Pigmented with a weak gold pigment
They are spherical cells
Form irregular cell clusters
Resistant to dry conditions and up to 10% NaCl
Can often be resistant to beta-lactam antibiotics

Question 3

What are the epidemiological features of staphylococcus aureus?

Answer 3

Ubiquitous
Colonization of anterior nares, moist folds of skins, oropharynx, gastrointestinal tract and urogenital tract
15% of normal healthy adults are persistant nasopharyngeal carriers
Higher numbers of carriers among hospital staff
Major cause of hospital acquired infection
Mainly transmitted by human-human and human-surface-human contact
Can survive on dry surfaces for long periods of time due to capsule

Question 4

What are the cytolysins that staphylocccus aureus can produce?

Answer 4

Alpha toxin, Beta toxin, Delta Toxin, Gamma Toxin,

Leukotoxin ED, Leukotoxin AB/GH, Gamma haemolysin, Panton-Valentine Leukocidin

Question 5

What are the functions of the alpha toxin produced by S.Aureus work?

Answer 5

Disrupts smooth muscle in blood vessels
toxic to many types of cells (leukocytes, erythrocytes and platlets)
Forms membrane pores

Question 6

What is the link between alpha toxin and ADAM 10?

Answer 6

ADAM 10 is used by alpha toxin as a receptor
ADAM 10 stands for a disintigrin and metalloproteinase domain containing protein 10 and acts as a cell surface protease
ADAM 10 is up regulated after alpha toxin binds to it

Question 7

How does beta toxin of S.Aureus function?

Answer 7

Also known as sphingomyelinase C this is a heat-laible protein which hydrolysis sphingomyelinase which is a membrane phospholipid
This disrupts the cell membrane making beta toxin toxic to a variety of cells

Question 8

What is the function of delta toxin produced by S.Aureus?

Answer 8

It is a toxin with wide spectrum cytolysin activity
Has surfactant, detergent-like action and amphipathic structure
Belongs to a family of phenol soluble modulins and is also produced by other staphylococci

Question 9

What is the interaction between beta and delta toxin produced by S.Aureus?

Answer 9

Beta toxin can hydrolyse the head of the phospholipid to provide better access to the hydrophobic tails for the delta toxin

Question 10

What are the features of gamma toxin produced by S.Aureus?

Answer 10

It is expressed by 99% of S.Aureus strains
The Gamma toxin locus expresses three proteins, two class S components and one class F allowing for two functional pairs of proteins HlgA+HlgB and HlgC+HlgB

Question 11

What are the features of panton-valetine leukocidin produced in S.Aureus?

Answer 11

Only produced by 5% of S.Aureus strains and is found in a phage encoded gene but in many Community acquired methicilin resistant S.Aureus
Panton-Valentine Leukocidin has been associated with necrotizing pneumonia but this is controversal

Question 12

What are the immunopathogenic factors of S.Aureus?

Answer 12

Peptidoglycan and lipoteichoic acid which are endotoxins which bind to Toll-Like receptors stimulating pro-inflammatory cytokines
Superantigens which cause oligo-clonal stimulation of T-Cells causing a massive release of pro-inflammatory cytokines and T cell mediators

Question 13

What are the immune evasion factors?

Answer 13

Capsule, Slime layer, Catalase, Clumping Factor, Protein A, toxins that interfere with the complement immune system

Question 14

What are the features of the capsule produced by S.Aureus?

Answer 14

A polysaccharide coat, outmost layer of the cell
Inhibits phagocytosis
Contains water which protects against desiccation
11 capsular subtypes are known

Question 15

What are the features of the slime layer produced by S.Aureus?

Answer 15

It is a loose bound water soluble film made up of monosaccharides and proteins
Biofilms on foreign bodies

Question 16

How is the catalase produced by S.Aureus used as an immune evasion factor?

Answer 16

Detoxifies peroxide and other free radical oxygen intermediate which is produced by macrophages

Question 17

How is the clumping factor of S.Aureus used as an immune evasion factor?

Answer 17

This is a bound coagulase which binds to fibrinogen in the blood and converts to insoluble fibrin
This fibrin then deposits on the cell surface prevents opsonisation and phagocytosis
Can also aid in cell aggregation

Question 18

How does protein A produced by S.Aureus act as an immune evasion factor?

Answer 18

This protein is produced by most S.Aureus but not other Staphylococci
It is a protein which is anchored to the cell wall, it binds almost all classes of IgG (not IgG3) in the wrong orientation by binding to the Fc region the prevents opsonisation and phagocytosis

Question 19

What is the role of staphylokinase in immune evasion?

Answer 19

Performs enzymatic conversion of plasminogen to plasmin

Plasmin can then cleave IgG, C3b and dissolve blood clots

Question 20

What are the forms of superficial skin diseases caused by S.Aureus?

Answer 20

Boils, impetigo and folliculitis

Question 21

What are the forms of invasive disease caused by S.Aureus?

Answer 21

pneumonia, endocarditis, deep abscess, bacteremia, osteomyelitis, spetic arthritis

Question 22

What are the forms of toxigenic diseases caused by S.Aureus?

Answer 22

Food poisoning, scalded skin syndrome

Question 23

What is impetigo?

Answer 23

localised cutaneous infection with pus-filled vesicles!

primarily affects young children

Question 24

What is folliculitis?

Answer 24

impetigo involving hair follicles

Question 25

What are furuncles or boils?

Answer 25

painful pus-filled cutaneous nodules!

Question 26

What is a carbuncle?

Answer 26

coalescence of furuncles, extension into subcutaneous tissue

can lead to systemic disease, bacteremia

Question 27

What is Staphylococcal Scalded Skin Syndrome?

Answer 27

cutaneous blisters followed by desquamation of epithelium
•  caused by action of exfoliative toxins
•  originally described by Gottfried Ritter (Ritter’s Disease)
•  affects primarily neonates and young children
•  low mortality rate, development of immunity

Question 28

What occurs in Staphylococcal Food Poisoning?

Answer 28

•  most common foodborne illness
•  results from contamination of food by human carrier and improper
food handling
•  microbial intoxication, not infection
•  caused by heat-stable enterotoxins (SEA, SEB, …)
•  severe vomiting, diarrhea, abdominal pain, nausea, sweating headache
•  rapid onset (hours), generally lasting for less than 24h

Question 29

What is bacteremia and acute endocarditis with regards to S.Aureus?

Answer 29

spread of bacteria into the blood from a focus of infection
•  >50% of cases are hospital acquired (surgery, contaminated catheters)!
•  bacteria can spread to other organs, particular the heart (endocarditis)!
•  S. aureus endocarditis has a mortality rate of nearly 50%!
•  damage to the endothelial lining of the heart, infected heart valve is coated!
with bacteria, platelets and cellular debris. Role of ClF-A?!
•  perforation of heart valve mainly by secreted enzymes, septic emboli !

Question 30

How does S.Aureus cause pneumonia?

Answer 30

after aspiration of oral secretion
•  consolidation and abscess formation in lung (cytotoxic
toxins!)
•  mostly in very young and in elderly

Question 31

What is necrotising pneumonia?

Answer 31

severe form of community-acquired pneumonia with septic
shock and high mortality (role of PV-leucocidin ?)
- epidemiologically linked to PVL producing strains

Question 32

What is toxic shock syndrome?

Answer 32

Localised growth of superantigen-producing strain

Question 33

What are the two types of toxic shock syndrome?

Answer 33

Menstrual toxic shock syndrome and non-menstrual toxic shock syndrome

Question 34

What is menstrual toxic shock syndrome?

Answer 34

Growth of a S.Aureus strain which produces a superantigen (specifically TSST as only this can penetrate the mucosal barrier) in the vagina
This can be caused by prolonged use of expandable tampons

Question 35

What is non-menstrual toxic shock syndrome?

Answer 35

Growth of a superantigen-producing strain in a wound, toxins are released into blood and cause systemic disease fever, hypotension, erythematous rash, multiple organ failure lack of protective antibodies against toxins appears to be a risk factor