MICROIMM Lec 25: Streptococcus pyogenes

Is Streptococcus G+ or G-?

G+

Is the genus Streptococcus motile?

No

Does Streptococcus form spores?

No

Describe the shape and arrangement of Streptoccus

Spherical cells, typically arranged in chains or pairs

Where can Streptococcus be found?

- Disseminated in the environment

- Colonizing humans and animals

Recently, an increase of cases of _______ and ______ infections caused by different species of Streptococcus have been found

Zoonotic and nosocomial

How many species are in the Streptococcus genus?

At least 100 different species

Streptococci are clinically divided into how many major categories?

3

List the 3 major categories of Streptococci

α-hemolytic

β-hemolytic

γ-hemolytic

Alpha = ____ hemolysis

Partial

Beta = ______ hemolysis

Complete

Gamma = _______ hemolysis

no

What are the different Streptococci lysing?

RBCs

What category is S. pneumoniae?

Alpha (partial hemolysis)

What category is S. pyogenes?

Beta (complete hemolysis)

What category is S. faecalis?

Gamma (no hemolysis)

Explain the name Streptococcus pyogenes

Strepto = chain

Coccus = round

Pyo = pus

Genes = forming

What is Group A strep (GAS)?

Another name for Strep pyogenes

Is this pathogen specific for humans or animals?

Human-specific pathogen

Does Strep pyogenes have a capsule?

Yes

Is Strep pyogenes invasive or not?

Can be both non-invasive or invasive infections

How is Strep transmitted?

Through airborne droplets, surfaces contaminated with bacteria, and skin contact

Strep (GAS) infections rank ____ among the 10 most deadly infectious diseases worldwide

5

What is Streptococcal pharyngitis?

strep throat

Non-invasive Strep throat infections are most common in age _____

children age 5-15 years

Describe the symptoms of strep throat

- Sore throat

- Pain with swallowing

- Fever

- Enlarged tonsils

- Red spots on the roof of the mouth

How can strep throat be diagnosed?

- Throat swab

- Analyze by a rapid strep test

The rapid strep test reports results within ______ of bacteria culture

15 mins

What is impetigo?

a common and highly contagious skin infection that mainly affects infants and young children

What age group is impetigo most prevalent in?

Most prevalent in children 2-5 years, but can occur at any age

Describe the symptoms of impetigo

- Erythematous (red) plaques

- With yellow crust

- Itchy, or painful

What is scarlatina?

another term for scarlet fever

Scarlet fever rashes are associated with bacterial _____

pharyngitis

Describe the symptoms of Scarlatina

- Sore throat

- Fever

- Red rash with a sandpaper-like feel

- Whitish coating on the surface of the tongue (strawberry)

What is responsible for the manifestation of these symptoms?

S. pyogenes exotoxin (superantigen)

Strep pharyngitis, impetigo, and scarlatina are all invasive/non-invasive infections

non-invasive

Is meningitis invasive or non-invasive infection?

Invasive

Describe the symptoms of meningitis

- Headache

- Neck stiffness

- Fever

- Altered mental status *

What fluid in our body is used to diagnose for meningitis?

Bacterial DNA from cerebrospinal fluid

Meningitis has a disease mortality rate of __ %

20%

Where does Strep bacteria get trapped?

Between the Meninges tissues covering the brain

What is necrotizing fasciitis?

Flesh-eating bacteria

Is necrotizing fasciitis invasive or not?

Invasive

Describe the symptoms of necrotizing fasciitis

- Aggressive (erthematous/gangrenous) skin

- Blisters

- Pus

- Swelling

- Soft tissue infection

- Necrosis of the muscle fascia and subcutaneous tissues

How is necrotizing fasciitis caused?

Can occur post-surgery, invasive procedures, or even a minor procedure

Is Streptoccocal toxic shock syndrome (STSS) invasive or not?

Invasive

Does STSS have a slow or rapid progression?

Rapid

STSS has the potential to culminate in what symptoms?

- Shock

- Multi-organ failure

- With an acute-elevated mortality

What virulence factors are being released by the bacteria to cause STSS?

Virulence factors: toxins, superantigens, bacterial proteins

Individuals who have multiple Strep pyogenes infections can develop ____ disorders

auto-immune

How many virulence factors does Strep bacteria have?

more than 30-40

What are the function of adherence virulence factors?

Helps bacteria attach to host or different components on the body

Name 3 examples of adherence virulence factors

- Capsule

- M protein

- Fibronectin binding proteins (FBPs)

What does Fibronectin binding proteins (FBPs) allow the bacteria to bind to?

fibronectin, a component of the extracellular matrix

What is the function of M protein?

prevents human phagocytes from attacking the bacteria

What does the capsule protect the bacteria from?

Recognition by immune system and phagocytosis

What are the functions of SLO and SLS virulence factors?

Pore formation - cell death

What are the functions of Streptococcal pyrogenic exotoxins?

Excessive activation of the immune system

What is another term for Streptococcal pyrogenic exotoxins?

Superantigens

Name an example of a disease that is caused by excessive activation of the immune system

Toxic shock syndrome

Name 2 examples of exotoxin virulence factors

- SLO and SLS

- Streptococcal pyrogenic exotoxins (superantigen)

Name 2 examples of immune modulation virulence factors

- Deoxyribonuclease (DNases)

- IgG-degrading enyzme (IdeS)

What are neutrophil extracellular traps (NETs) made of?

DNA and protein

What is the function of Deoxyribonuclease (DNases)?

Degradation of neutrophil extracellular traps (NETs)

What is the function of IgG-degrading enzyme

Cleaves IgG antibodies

What happens to the cleaved antibodies?

Unable to opsonize and neutralize bacteria

Define exoenzyme

enzymes produced inside the bacteria but are secreted to work outside the bacteria cell

Name 1 example of an exoenzyme virulence factor

Streptococcal pyrogenic exotoxin B (SpeB)

What is the function of Streptococcal pyrogenic exotoxin B (SpeB)?

Cleaves a wide range of host and bacterial proteins; target and degrade host tissues and proteins

List the 4 steps of GAS Pathogenesis

1. Adhesion

2. Invasion

3. Immune evasion

4. Dissemination

How many different serotypes of M protein are there?

>250

Each serotype has a different ______

virulence factor/characteristic

Where does the M protein reside in the bacteria?

On cell surface

What membranes/layers does the M protein cross?

- Hyaluronic acid capsule

- Peptidoglycan layer

- Cytoplasmic membrane

There are at least ___ superantigens in S. pyogenes

16

What is a cytokine storm caused by?

Superantigen molecules linked to the activation of T cells

With conventional T cell activation, ____% of the T cell is activated

~0.01%

With superantigen-mediated T cell activation, __% of the T cell is activated

>20%

What 2 molecules does superantigen interact and bridges between?

MHC-II on APC and TCR on T cells

Superantigens are responsible for the establishment of infections and ______

scarlet fever

What is the name of the new sublineage that resulted in a 21-fold increase of scarlet fever cases?

M1_UK

The new sublineage M1_UK has ___ chromosomal mutations

27

The M1_UK sublineage is characterized by a 10-fold increase in what superantigen?

SpeA superantigen

What class of antibiotics is used to treat Strep?

B-lactams

What B-lactam antibiotic is specifically used to treat Strep?

Amoxicillin

Treatment with amoxicillin is a __-___ day course

6-10 days

What are the alternative antibiotics used for patients with amoxicillin hypersensitivity (Rash)?

- Clindamycin

- Erthromycin

- Clarithromycin

Are there any confirmed reports of B-lactams resistance?

no

Is there an available vaccine against GAS?

no

What is M protein structurally similar to?

Collagen present on host

S. pyogenes vaccines have the potential to vaccine-induce what disease?

rheumatic heart disease

Define auto-antibodies

proteins produced by the immune system that attack the body's own cells, tissues, and proteins

Antibodies produced by the body to attack M protein can end up attacking _____

collagen or other host self molecules

What age group is most susceptible to rheumatic heart disease (RHD)?

Pediatric

The disease results from damage to _____

heart valves

Which 2 specific heart valves are damaged?

Mitral and aortic

What is the only approved treatment for RHD?

Valve replacement

Autoantibodies will mistake Strep pyogenes cell wall components with the host's ______

heart proteins

Can regular mice be colonized intranasally (administered through the nose)?

No

What type of mice do they use instead to test S. pyogenes?

humanized mice