Lecture 9 - Streptococcal Respiratory Infections Flashcards
(100 cards)
1
Q
5 characteristics of streptococci?
A
- Gram-positive cocci (cells may be ovoid or bullet-shaped) that grow in chains
- Catalase-negative: important in distinguishing them from staphylococcus genus (also gram + cocci)
- Widely distributed in nature: found in milk, dairy products, water, dust and vegetation
- Normal inhabitants of the upper respiratory tract and intestinal tract and other mucosal surfaces of man and various animal
- Majority of streptococci are saprophytic and nonpathogenic but some are opportunistic or overt pathogens
2
Q
How to culture streptococci?
A
- 24-48 h incubation at 37°C in 5% CO2 in air = capnophilic
- Ferment a variety of carbohydrates producing lactic acid as the major fermentation end-product = homolactic fermenters, even if O2 in the environment
3
Q
What are the 3 types of hemolyses produced by streptococcal colonies growing on blood agar
A
- Incomplete hemolysis: alpha (α) hemolysis
- Complete hemolysis: beta (β) hemolysis
- Not hemolytic: “gamma” (γ) hemolysis
4
Q
4 groups of streptococci?
A
- Pyogenic group: produce pus
- “Viridans” group: alpha-hemolytic
- Enterococcus group => its own genus
- Lactic group: used in dairy industry => actually their own lactococcus genus
5
Q
3 ways of classifying streptococci? Which is most reliable?
A
- Hemolysis type
- 4 groups
- ***Lancefield system based on the antigenic characteristics of the group-specific ‘C substance’ (Lancefield group A, B, C, D, etc.) which are cell wall polysaccharides or teichoic acids
6
Q
Envelope composition of streptococci?
A
Thick cross-linked peptidoglycans
7
Q
What is the principle virulence factor of GAS (Group A streptococci)?
A
M protein
8
Q
How many different immunologically distinct types of M proteins? What does this mean? What to note?
A
Over 200 => highly immunologically variable
NOTE: immunity is M type specific (memory immunity will only be to the one type of M protein that you have been exposed to)
9
Q
Describe the M protein. Role?
A
α-helical coiled-coil fibrillar protein that has a domain-like structure with the AA sequence of the extracellular portion highly variable => involved in immune evasion (antiphagocytic and degrades complement component C3b) and adhesion
10
Q
2 classes of M proteins? Describe each.
A
- Class I: share extracellular epitopes but strains do not produce opacity factor
- Class II: lack shared epitopes, but strains produce opacity factor
11
Q
Which M proteins cause rheumatic fever?
A
Class I only
12
Q
What are 2 diseases resulting from local infection with GAS and their products? What can each progress to?
A
- Mucosal infection: streptococcal sore throat scarlet fever rash from erythrogenic toxin (bacteriophage encoded) => may proceed to ARF or AGN
- Skin infection: streptococcal pyoderma => may proceed to AGN
13
Q
What are 4 diseases resulting from invasion of GAS?
A
- Erysipelas: skin infection, typically on lower limbs with blistering and sharp demarcations
- Puerperal fever: uterus infection
- Sepsis from traumatic or surgical wounds infections
- Toxic-shock syndrome and necrotizing infections/fasciitis
14
Q
3 M protein types involved in toxic-shock syndrome and necrotizing infections/fasciitis?
A
M1, M3, M5
15
Q
What is post-streptococcal disease?
A
- Pharyngeal infections => rheumatic fever OR glomerulonephritis
- Skin infections => only acute glomerulonephritis
16
Q
What is acute glomerulonephritis from post-streptococcal disease characterized by? Cause?
A
- Edema
- HT
- Hematuria
- Proteinuria
Cause: deposition of immune complexes in the renal glomeruli (Type III immunopathology)
17
Q
Onset of acute glomerulonephritis from post-streptococcal disease?
A
~10 days following a skin infection
18
Q
How does acute glomerulonephritis from post-streptococcal disease heal?
A
Spontaneous healing over weeks to months
19
Q
What can progressive course of acute glomerulonephritis from post-streptococcal disease lead to?
A
Renal failure, congestive heart failure, and death
20
Q
What is rheumatic fever from post-streptococcal disease characterized by?
A
- Valvulitis
- Pericarditis
- Myocarditis
- Erythema marginatum
- Arthritis/arthralgias
- Aschoff nodules (subcutaneous)
- PANDAS = pediatric autoimmune neurologic disorder associated with streptococci (CNS)
21
Q
Describe molecular mimicry of GAS.
A
The group A carbohydrate and M protein are the main cross-reactive antigens with:
HEART
- Myocardium and valve endothelium
- Myosin, laminin, keratin
BRAIN
- Lysoganglioside and tubulin
- Dopamine D2 and D1 receptors
22
Q
5 M types associated with rheumatic fever?
A
M3, M5, M18, M19, M24
23
Q
5 M types associated with glomerulonephritis?
A
M49, 57, M59-61
24
Q
Describe antibodies against GAS?
A
Anti-M antibodies are opsonic (promote phagocytosis)
25
What is the most common form of bacterial pneumonia?
Streptococcus pneumoniae
26
Reservoir of Streptococcus pneumoniae?
Nasopharynx
27
Carrier rate of Streptococcus pneumoniae? What to note?
May be as high as 60%
NOTE: as individuals get older the periods of carriage become shorter and intervals in between become longer
28
Are all Streptococcus pneumoniae capsule types equally invasive?
NOPE
29
Is Streptococcus pneumoniae usually a primary infection? What does this mean?
NOPE
Usually infects a respiratory tree primarily infected by a viral infection
30
What is the major line of defense against Streptococcus pneumoniae? What to note?
PMNs
NOTE: opsonic antibodies are important as well
31
Describe antibodies against Streptococcus pneumoniae.
Capsule-type specific (up to ~ 100 types of capsules )
32
What does the enzyme catalase do?
Breaks down hydrogen peroxide to O2 and H2O
33
What does saprophytic mean?
Deriving its nourishment from dead or decaying organic matter
34
Other name for alpha hemolysis?
Greening hemolysis
35
Group of streptococci that conduct alpha hemolysis?
“Viridans” group
36
Hemolysis type of Streptococcus pneumoniae?
Alpha hemolytic
37
Hemolysis type of GAS?
Beta hemolytic
38
Most important Lancefield groups in humans?
A, B, C, D, and G
39
Which streptococci species can be classified in the Lancefield system?
Only non- and beta-hemolytic streptococci
40
Proper name of GAS?
Streptococcus pyogenes
41
Other name for Streptococcus pneumoniae?
Pneumococcus
42
4 tests to identify GAS? Which is determinative?
1. Gram stains => should be +
2. Catalase test => should be -
3. Bacitracin antibiotic test on blood agar plate => should be + with clear zone surrounding the disk
4. ***Antibodies against Lancefield antigen: latex beads coated with antibodies to which a drop of specimen is added in suspension => if positive latex beads will cross-link when binding to antigen => agglutination
43
How does the catalase test work?
Take tiny piece of colony and smear on microscope slide, then add a drop of hydrogen peroxide => immediate fizzing/bubbling is a positive test
44
Most common cause of bacterial pharyngitis? What to note?
GAS infection
NOTE: almost all pharyngites are viral though
45
Incubation time for bacitracin test for GAS?
48 h
46
When testing for GAS, if the Lanfield antigen antibody test is negative, what should you do?
Bacitracin antibiotic test on blood agar plate
47
Treatment for GAS infections?
Penicillin
48
Envelope composition of GAS?
1. Capsule: hyaluronic acid with low immunogenicity
| 2. Cell wall: protein antigens M, T, R, and E
49
Do both GAS and Streptococcus pneumoniae have a capsule?
YUP
50
What are the 14 virulence factors of GAS?
1. Capsule
2. Lipoteichoic acid
3. M protein
4. M-like proteins
5. F protein
6. Pyrogenic exotoxins
7. Streptolysin S
8. Streptolysin O
9. Streptokinase
10. DNase
11. C5a peptidase
12. Opacity factor
13. G3PD
14. Enolase
51
How is the GAS capsule virulent?
Antiphagocytic and complement inactivating
52
How is the GAS lipoteichoic virulent?
Binds to epithelial cells
53
How is the GAS F protein virulent? What does it stand for?
Mediates adherence to epithelial cells
Fibernectin protein
54
Do GAS express all 14 virulence factors at all times?
NOPE
55
How are the GAS M-like proteins virulent?
Bind immunoglobulins M and G and alpha2-macroglobulins (protease inhibitors)
56
How are the GAS pyrogenic exotoxins virulent? 6
1. Mediate pyrogenicity
2. Enhancement of delayed hypersensitivity and susceptibility to endotoxin,
3. Cytotoxicity
4. Nonspecific mitogenicity for T cells (all CD4 T cells = superantigens)
5. Immunosuppression of B-cell function
6. Production of scarlatiniform rash
57
3 examples of GAS pyrogenic exotoxins? How many total?
SpeA, SpeB, SpeC
May be as many as 13
58
How the GAS streptolysins S and O virulent? 3
1. Lyse leukocytes, platelets, and erythrocytes
2. Stimulate release of lysosomal enzymes
3. Immunogenic
59
How is the GAS steptokinase virulent? 2
1. Lyses blood clots
| 2. Faciliates spread of bacteria in tissues
60
How is the GAS DNase virulent? 2
1. Depolymerizes cell-free DNA in purulent material
| 2. Interferes with NETs = neutrophil extracellular traps
61
How is the GAS C5a peptidase virulent?
Degrades C5a, which is the most important chemokine of the complement cascade
62
How is the GAS opacity factor virulent? What is it? 2
Lipoproteinase
1. Increases opacity of serum
2. Binds fibronectin
63
How is the GAS G3PD virulent? Where is it located?
Acts as an adhesin
Located at cell surface
64
How is the GAS enolase virulent? Where is it located?
Binds plasminogen
Located at cell surface
65
What do both GAS G3PD and enolase have in common?
Both in glycolytic pathway
66
What happens if you knock down GAS M protein?
GAS is essentially non-virulent
67
4 types of pathogeneses of GAS infections?
1. Diseases resulting from local infection with GAS and their products
2. Diseases resulting from invasion of GAS
3. Infective endocarditis
4. Post-streptococcal disease
68
Clinical manifestation of streptococcal sore throat scarlet fever rash? 2
1. Strawberry colored tongue with pale color around mouth = circumoral pallor
2. Sand-paper like rashes on trunk and limbs
69
Other name for streptococcal pyoderma?
Impetigo
70
5 M types of streptococcal pyoderma?
M types 49, 57, 59-61
71
Common co-infection with streptococcal pyoderma?
With staphylococcus aureus
72
Population at risk of streptococcal pyoderma?
Kids starting school
73
Clinical manifestation of streptococcal pyoderma?
Honey-crusted lesions
74
Which skin infection is deeper in the dermis: impetigo or erysipelas?
Erysipelas
75
Other name for puerperal fever?
Childbed fever
76
Other bacteria that cause puerperal fever?
GBS
77
Why can invasive GAS infections lead to toxic-shock syndrome?
Due to the superantigenicity of the pyrogenic exotoxins produced by GAS
78
Why do certain patients that have GAS pharyngitis develop acute rheumatic fever?
Some individuals are susceptible to this because of the particular T cell repertoire they have and their particular MHCs that enable them to recognize certain peptides
79
Disease type of acute rheumatic fever?
Musculoskeletal disease
80
Does acute rheumatic fever affect all layers of the heart?
YUP
81
Pathogenesis of acute rheumatic fever?
Antibodies against streptococcus are cross-reacting with host tissues
82
Gell and Coombs classification for acute rheumatic fever?
Type II
83
How to make an acute rheumatic fever diagnosis?
Test blood for high titers of antibodies against streptolysin O => > 250 units indicates recent or repeated infections
84
Long-term effect of acute rheumatic fever? Implication?
Permanent cardiac scarring, especially the valves => more susceptible to be colonized by any bacteria in the blood
85
Long-term effect of acute glomerulonephritis?
NONE
86
Immunity against the erythrogenic toxins in GAS infections? What to note?
Neutralized by antitoxins
NOTE: no effect on infection
87
What GAS immunity follows infection?
Antibodies against streptolysin O
88
GAS infection diagnostic tool?
Anti-DNAse antibodies
89
How to make an acute glomerulonephritis diagnosis?
Anti-DNAse antibodies
90
Transmission of GAS infections?
Transmission from one infected person to the other (horizontal transfer), as it is not carried asymptomatically
91
Can Streptococcus pneumoniae be asymptomatic?
YUP
92
3 tests to identify Streptococcus pneumoniae?
1. Gram stains => should be +
2. Catalase test => should be -
3. Optochin (detergent = O-disk) OR bile test on blood agar plate => cell wall undergoes lysis due to activation of cell wall transpeptidases (autolysins) => should be + with clear zone surrounding the disk
93
Specimen to send to lab for testing for Streptococcus pneumoniae?
Sputum sample
94
What is special about the Streptococcus pneumoniae capsule?
It is produced on blood agar plate (not usually the case) => colonies have a mucoid appearance
95
How to differentiate Streptococcus pneumoniae from all of the viridans streptococci that are residents in the oralpharynx? Why?
O-disk/bile disk because all of them are resistant to optochin/bile
96
Most important virulence factor of Streptococcus pneumoniae?
Cps = polysaccharide capsule
97
Why are virulence factors not as relevant in Streptococcus pneumoniae? Implication?
Because the virulence is caused by the immune response against the pathogen: pathogen + detergents => lysis releasing pro-inflammatory molecules associated with the gram + cell wall (e.g. proteoglycans, lipoteichoic acid, wall teichoic acid), which are PAMPs
Implication: naturally acquired immunity is high with opsonic antibodies, which are capsule specific
98
3 diseases caused by Streptococcus pneumoniae?
1. Pneumonia
2. Middle ear infections = otitis media
3. Meningitis
99
What is special about Streptococcus pneumoniae immunity?
Immunity transferred from mother to neonate with IgGs for 3-5 weeks postpartum, which is important while the newborn ramps up his own immune system
100
2 vaccines for Streptococcus pneumoniae? What to note?
1. Polyvalent conjugated capsular polysaccharide with proteins that are virulent factors for other bacteria (e.g. exotoxins) = T-dependent antigen (13 capsule types)
2. 23 capsule types (most virulent ones) protecting against 90% of pneumococcal infections
NOTE: #2 does not work in neonates and the elderly because polysaccharide antigens are T-independent (Ti2) and induce IgMs, which newborns/elderly cannot handle
