streptococcus pyogenes Flashcards

1
Q

describe the streptococcus genus. what type of bacteria?

A

gram+, spherical – typically in chains or pairs (one plane)

non-motile

doesn’t form spores

recently , an increase of cases of zoonotic and nosocomial infections caused by different species of Streptococcus have been reported

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2
Q

how are species in the streptococci genus categorized?

A

initially classified by their pattern of hemolysis on blood agar

(α) alpha-hemolytic
— partial hemolysis
e.g. streptococcus pneumoniae

(β) beta-hemolytic
— total hemolysis
e.g. streptococcus pyogenes

(γ) gamma-hemolytic
— no hemolysis
e.g. streptococcus faecalis

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3
Q

describe streptococcus pyogenes

A

also called group A streptococcus

under beta-hemolytic category

human-specific pathogen

either non-invasive or invasive infections

encapsulated

produces many virulence factors and is able to inhibit innate immunity!

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4
Q

what does streptococcus pyogenes cause? what is it a common cause of today? what are some severe diseases it causes? what are some mortal causes it has had historically?

A

today, a common cause of pharyngitis (i.e. strep throat) and impetigo

severe invasive streptococcal disease

streptococcal toxic shock syndrome (“flesh-eating” disease)
— very aggressive infection that can target healthy people

post-infection sequelae = acute rheumatic fever
— occurs after infection, caused by immune response

historically, a major cause of mortality due to
— scarlet fever
— puerperal sepsis (infection of mother during childbirth)
— wound infections in soldiers

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5
Q

how is streptococcus pyogene transmitted?

A

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

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6
Q

describe the disease: streptococcal pharyngitis. common demographic? symptoms? how’s it diagnosed? treatment?

A

aka strep throat; non invasive!

most common in children aged 5 - 15 years

symptoms
– sore throat
– pain with swallowing
– fever
– enlarged tonsils
– red spots on the roof of the mouth

diagnosis
– throat swab which can be analyzed by a rapid strep test that reports results within about 15 minutes
———- positive test means antibiotic use
– bacteria culture

treatment
– beta-lactams (no documented resistance - until recently!)
– erythromycin (resistant strains exist)

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7
Q

describe impetigo. caused by what bacteria? common demographic? symptoms? treatment?

A

streptococcus pyogenes but also streptococcus aureus

common infection and contagious

non-invasive

most prevalent in children aged 2-5 but can occur at any age

symptoms
– erythematous plaques with a yellow crust
– itchy
– painful

treatment
– topical antibiotics

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8
Q

describe scarlet fever. caused by what bacteria? symptoms?

A

aka scarlatina

rash associated with bacterial pharyngitis

caused by streptococcus pyogenes – its exotoxins (superantigens) are mainly responsible for the manifestation

symptoms
— sore throat
— fever
— red rash with sandpaper-like feel
— and a whitish coating on the surface of the tongue (strawberry-like)

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9
Q

how is meningitis diagnosed for?

A

positive culture or bacterial DNA of cerebrospinal fluid

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10
Q

what are the non-invasive and invasive infections caused by streptococcus pyogenes?

A

non-invasive
— streptococcal pharyngitis (strep throat)
— impetigo
— scarlet fever (scarlatina)

invasive
— meningitis
— necrotizing fasciitis (flesh-eating)
— streptococcal toxic shock syndrome (STSS)

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11
Q

describe necrotizing fasciitis

A

necrotizing fasciitis is a subset of aggressive skin and soft tissue infection that cause necrosis of the muscle fascia and subcutaneous
tissues

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

these patients are extremely ill and should be transferred
immediately to the intensive care unit

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12
Q

describe streptococcal toxic shock syndrome (STSS)

A

manifests with rapid progression and has the potential to culminate in shock, multi-organ failure, and with an acute-elevated mortality

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13
Q

what are the virulence factors (and their components) of streptococcus pyogenes?

A

adherence
— M proteins binds to C4 proteins to protect itself from complement system (anti-phagocytosis)
— fibronectin proteins
— capsule

exotoxins
— super antigens (streptococcal pyrogenic exotoxins) excessively activate the immune system
— SLO and SLS (streptolysin S) form pores, leading to cell death

immune modulation
— DNases (deoxyribonucleases) degradation of neutrophil extracellular traps (NETs)
— IgG-degrading enzymes (IdeS) cleaves antibodies

exoenzyme
— streptococcal pyrogenic exotoxin B (SpeB) cleaves a wide range of host and bacterial proteins

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14
Q

describe M proteins. how is the M protein a virulence factor?

A

M proteins binds to C4 proteins to protect itself from complement system (anti-phagocytosis)

also related to adhesion!

used to seroclassify the species: streptococcus pyogene
—- there are more than 250 different serotypes of M proteins

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15
Q

describe GAS (group A streptococcus) pathogenesis

A

adhesion
— attaches to pharyngeal epithelium or skin surface
— facilitated by M protein and the pathogen’s capsule which binds to specific glycan structures and CD44 on the epithelial cells

invasion
— invades epithelial cells
— facilitated by streptococcal pyrogenic exotoxin B (SpeB) (cleaves) and SLS (pore former) which destabilizes junctional proteins of the epithelial cells

immune evasion
— evades phagocytosis via M proteins, exotoxins (superantigens), and immune modulation (DNases, IgG-degrading enzymes)

dissemination

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16
Q

describe super antigens (SpeB). how is it a virulence factor for streptococcus pyogene?

A

there are at least 16 superantigens in streptococcus pyogenes

responsible for the establishment of infections and scarlet fever

function as T cell activators by hyper activating adaptive immune system, resulting in cytokine storm
— disease: toxic shock syndrome, also made by streptococcus aureus

17
Q

what is M1uk?

A

a new sub-lineage of streptococcus pyogenes that was responsible for the increased incidence of scarlet fever and invasive infections in 2019

it has 27 chromosomal mutations

characterized by a 10-fold increase in the SpeA superantigen

18
Q

describe super antigens DNases. how is it a virulence factor for streptococcus pyogene?

A

breaks down the chromatin in the neutrophil extracellular traps to evade the immune system

19
Q

what is the treatment of streptococcus pyogenes?

A

6 to 10 day course of amoxicillin (beta-lactams) is the mainstay

patients with amoxicillin hypersensitivity (rash) requiring antibiotics
should receive 10 days clindamycin, Erythromycin, or clarithromycin.
—– no confirmed reports of beta-lactams resistance

no available vaccine against GAS
—– currently eight candidates in medical trials.
—– S. pyogenes vaccines, including the potential for vaccine-induced Rheumatic Heart Disease due to auto-antibodies.

20
Q

what is rheumatic heart disease?

A

most commonly acquired heart disease

block blood flow or blood flows backwards

results from damage to heart valves (mitral or aortic)
—- an be caused by autoantibodies that cross-react with human and streptococcal proteins

has an autoimmune-inflammatory nature

34 million people were estimated to be living with the disease

often follows cases of acute rheumatic fever

21
Q

describe the humanized mouse model, what did it tell us?

A

S. pyogenes is a human-specific pathogen

regular mice cannot be colonized intranasally as superantigens do not bind to their MHC II well

but humanized mice possess a MHC class II molecule similar to that found in humans. allowing the infection to establish in mice

MHC II is an important contributor to host specific tropism by streptococcus pyogenes

AND

superantigens should be considered further as valid vaccine candidates to target the commensal state of streptococcus pyogenes

AND

functional T cells are required for nasopharyngeal infection by streptococcus pyogenes