Lecture 6: Streptococci and Disease Flashcards
is strep gram + or -
gram +
how do strep often grow
in chains, some produce capsules
can strep be treated with penicillin
yes - no beta lacatmase gene found
how are streptococci classified
by serologic specificity of cell wall group specific carbohydrates
where can strep be found
asymptomatic colonisation of upper respiratory tract (~20% carriers)
how is strep transmitted
human to human, respiratory droplets, wound infections
incidence in populations
highest in maori and pacific island populations
the species can be further divided into different ____ based on variations in the ____
M serotypes, M protein
List the strep virulence factors
Adhesins, Pili, Cytolysins, Spreading factors, Superantigens, Immune evasion factors
MSCRAMMS
Microbial surface components recognizing adhesive matrix molecules
explain how adhesins/MSCRAMMS work
- cell wall-attached proteins found in Gram-positive bacteria
- bind to host extracellular matrix proteins eg. fibronectin, elastin, laminin, vitronectin and collagen.
- important for tissue colonization.
- Examples are M protein (binds to fibronectin,
fibrinogen, CD46), F protein (binds to fibronectin) and Cpa (collagen-binding protein).
Explain how Pili work
- long hair-like structures protruding from cell surface. - - cell wall-anchored
- built from covalently assembled protein monomers that form the pilus fiber.
- A tip protein is believed to function as an adhesin
- Pili have also been implicated in cell
aggregation (biofilm formation).
What are the two cytolsins in strep
streptolysin O
streptolysin S
Streptolysin O
(SLO): oxygen-labile cytolysin that forms pores in host cell membrane
Streptolysin S
- (SLS): oxygen-stable cytolysin
- lyses leucocytes, erys and platelets.
- Completely lyses red blood cells = β-hemolysis.
- highly antigenic
- anti-SLO antibodies are tested for diagnostic of previous S. pyogenes infection in suspected cases of acute rheumatic fever.
what are spreading factors
proteins that facilitate spreading from a localized infection (e.g., abscess) to surrounding tissue or blood (causing bacteremia).
give examples of spreading factors
lipases, nucelases, hyaluronidase, proteases, streptokinase (fibrinolysin)
lipases
hydrolyse lipids, for invasion of cutaneous tissues
nucleases
hydrolyses DNA, decrease viscosity of pus
hyaluronidase
hydrolyses hyaluronic acid in connective tissue
proteases
streptococcal cysteine protease (SCP) with wide substrate spectrum
Streptokinase (fibrinolysin)
causes fibrinolysis (dissolves clots)
The streptococcal SAgs are ____ and ____ related to the staphylococcal superantigens, however, they do not cause ____ (in contrast to some staphylococcal
SAgs). SAgs trigger massive release of ____ (TNF-α, IFN-γ) and over-stimulation of the host ____, resulting in systemic ____.
structurally, functionally, food poisoning, pro-inflammatory cytokines, immune response, inflammation
What are the immune evasion factors of strep
capsule, m protein, C5a peptidase
capsule
a dense hyaluronic acid coat that prevents opsonisation with ab and complement
(inhibits phagocytosis). Only in some strains
M-protein
in addition to its function as an adhesin, M protein prevents complement factor
C3b from opsonising (antiphagocytic).
C5a peptidase
a protease that cleaves complement factor C5a (a chemoattractant) preventing neutrophil migration to the site of infection.
S. pyogenes and diseases
impetigo, pharyngitis, scarlet fever, cellulitis, necrotising fasciitis (flesh eating disease), Sreptococcal toxic shock syndrome (STSS), rheumatic fever and rheumatic heart disease
pyoderma/Impetigo
- localised purulent cutaneous infection
- S. pyogenes colonisaition after contact with inferted person or fomites
- subcutaneous tissue infection through breaks in skin
- Highly communicable
- crowded places with hot/humid climate.
- kids most affected
Pharyngitis
- develops 2-4 days after exposure to S. pyogenes.
- sore throat, fever, reddened pharynx, tonsillitis, pus filled vesicles on tonsils.
Scarlet fever
- complication of pharyngitis
- can develop into serious systemic disease.
- Caused by strains that produce the superantigen pyrogenic exotoxin A (SPE-A) = “scarlet fever toxin”. = superantigen
- fever, sore trhoat, “strawberry tongue”, rash on chest
Cellulitis
- infection of skin that involves subcutaneous tissue.
- acute and rapidly spreading infection (hyaluronidase, DNAse)
Necrotising fasciitis (flesh eating disease)
- deep infection of the skin, involves destruction of muscles.
- S. pyogenes is introduced through e.g., minor cuts, trauma, burn, surgery or vesicular viral infection.
- deep tissue infection is supported by spreading factors (DNAses, proteases, and hyaluronidase)
- often develops into severe systemic disease with high mortality (toxic shock syndrome).
STSS: often follows ____ and ____.
STSS has a mortality rate of ____ (more severe than staphylococcal TS). Massive release
of ____ occurs in response to ____ secretion. Overstimulation of the immune response leads to ____. Symptoms include ____, ____, ____ and ____.
necrotising fasciitis, sepsis, 30-70%, pro-inflammatory cytokines, superantigen, systemic inflammation, fever, headace, multiorgan failure, shock
Rheumatic Fever and Rheumatic Heart Disease:
Develops after ____ due to S. pyogenes. Inflammation of
endocardium, myocardium, pericardium results in thickened and deformed ____ and
____ in myocardium. The disease often starts with ____in joints
(arthritis).
ARF is an ____, NOT an infection! It is triggered by ____, an antibody cross-reaction where antibodies generated against the M protein also bind (cross-
react) to ____ (cardiac myosin, collagen in joints, …). This triggers a ____ immune response.
untreated/chronic sore throats, heart valves, granulomas, inflammatory changes, autoimmune disease, molecular mimicry, host proteins, type II hypersensitivity
S. agalactiae (group B streptococcus)
A gram-positive coccus that grows in long chains. It is either β-hemolytic or non-hemolytic and carries the Lancefield group B specific carbohydrate.
S. agalactiae (group B streptococcus)
A gram-positive coccus that grows in long chains. It is either β-hemolytic or non-hemolytic and carries the Lancefield group B specific carbohydrate.
group B streptococcus causes ____ of ____ and ____. Most infections in newborns are acquired from mother during ____ or at ____.
asymptomatic colonisation, upper respiratory, genitourinary, pregnancy, time of birth
neonatal disease of s. agalactiae (GBS)
pneumonia, becteremia, sepsis, menigitis
infections in pregnant women (GBS)
UTI, bacteremia
viridans streptococci
Asymptomatic colonisation of oropharynx, gastrointestinal tract and genitourinary tract.
Commensales of mouth flora (S. mitis, S. mutants, …)
virulence factors of viridans strep
Less virulent than S. pyogenes (less immune evasion toxins). Some carry adhesins/pili for
binding to teeth, biofilm (dental plaque).
Viridans strep diseases
- dental caries: S. mutants, S. sobrinus
- bacterial endocarditis: S. gordonii, S. mitis
- septic shock in immuno-compromised patients
Streptococcus pneumoniae shape
Lancet-shaped’ diplococci or short chains. Most strains have outer capsule
strep penumoniae epidemiology
Endogenous spread from colonised pharynx to lungs, sinuses, ears, …
Conditions that interfere with bacterial clearance are risk factors (e.g.,
immunocompromised patients)
Streptococcus pneumoniae - virulence
S.pneumoniae carries antiphagocytic capsule and produces pneumolysin, a cytolysin that
destroys ciliated epithelial cells.
Streptococcus pneumoniae - diseases
- Pneumonia (60% of bacterial pneumonias), agzer aspiration, bacteria multiply in alveolar space, infiltration of neutrophils and alveolar machrohages, inflammaion (most damage caused by immune response), symptoms: fever, yellowish sputum, chest pain
- Meningitis: headache, fever, sepsis, high mortality
- Bacteremia: more common in patients with meningitis
- sinusitus and otitis media: usually after virus infection
rheumatic fever and rheumatic heart disease mechanism
conserved region in GAS protein structurally resembles certain host antigen (molecular mimicry)
GAS - group a strep. RF is Autoimmune disease
molecular mimicry
different proteins share antibody epitopde
epitope
small region with a protein or sugar that us recognized by an antibody or T cell receptor
RF autoimmune anitbody reaction
s. pyogenes, m protein, antibody binding
antibody cross reaction to protein from eg. cardiac myofibre (note, - this is not M protein but a different ptotein that is structurally similar)
antibody rects with own tissue
causes RF
explain how Acute rheumatic fever (ARF) comes about
- cross reactive antibodies trigger a type II hypersensitivity reaction
explain type II hypersensitivity reaction
- neutrophil adherence to host tissue
- frustrated phagocytosis - cant phagocytose large tissue
- extracellular enzyme release
explain the normal antimicrobial action
- microbe opsonised by c3b and labeled for destruction
- phacoytes like neutrophils have Fc receptro for andtibody adn C3b receptor to bind to C3b
- phagocytsis
- lysosome fusion
streptococcus pneumonia - shape
gram - postive diplococcus
pneumonia risk factors and incidence
30-60% children and <10% carriers
- young age, close contact, viral inections
