streptococcus pyogenes Flashcards
describe the streptococcus genus. what type of bacteria?
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
how are species in the streptococci genus categorized?
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
describe streptococcus pyogenes
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!
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?
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
how is streptococcus pyogene transmitted?
thru airborne droplets, surfaces contaminated with bacteria, and skin contact
describe the disease: streptococcal pharyngitis. common demographic? symptoms? how’s it diagnosed? treatment?
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)
describe impetigo. caused by what bacteria? common demographic? symptoms? treatment?
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
describe scarlet fever. caused by what bacteria? symptoms?
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)
how is meningitis diagnosed for?
positive culture or bacterial DNA of cerebrospinal fluid
what are the non-invasive and invasive infections caused by streptococcus pyogenes?
non-invasive
— streptococcal pharyngitis (strep throat)
— impetigo
— scarlet fever (scarlatina)
invasive
— meningitis
— necrotizing fasciitis (flesh-eating)
— streptococcal toxic shock syndrome (STSS)
describe necrotizing fasciitis
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
describe streptococcal toxic shock syndrome (STSS)
manifests with rapid progression and has the potential to culminate in shock, multi-organ failure, and with an acute-elevated mortality
what are the virulence factors (and their components) of streptococcus pyogenes?
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
describe M proteins. how is the M protein a virulence factor?
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
describe GAS (group A streptococcus) pathogenesis
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
describe super antigens (SpeB). how is it a virulence factor for streptococcus pyogene?
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
what is M1uk?
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
describe super antigens DNases. how is it a virulence factor for streptococcus pyogene?
breaks down the chromatin in the neutrophil extracellular traps to evade the immune system
what is the treatment of streptococcus pyogenes?
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.
what is rheumatic heart disease?
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
describe the humanized mouse model, what did it tell us?
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
