Streptococcus pyogenes (Group A Strep)

Definitions & Key takeaways

Streptococcus pyogenes, often called group A streptococcus (GAS), is a gram-positive, beta-hemolytic, and bacitracin-sensitive bacteria. Group A streptococcus normally colonize the pharynx, vagina, or the skin, where they're part of the normal flora, but in some cases, they may take advantage of a weakened immune system and causes infections like strep pharyngitis, scarlet fever, impetigo, necrotizing fasciitis. Infections due to certain strains of this bacteria can involve certain bacterial toxins, leading to scarlet fever or toxic shock syndrome. Group A streptococcus is also associated with post-infectious sequelae, like acute rheumatic fever and post-streptococcal glomerulonephritis. Treatment involves antibiotics like penicillin G, cephalosporins such as ceftriaxone, and macrolides such as azithromycin.

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Introduction 0:00–0:35

Streptococcus pyogenes, sometimes called Strep pyogenes, can be broken down into “strepto” which means chain, “coccus”, which refers to round shape, “pyo” which means pus, and “genes” which refers to forming.
So, Strep pyogenes are round bacteria that grow in chains, responsible for a number of infections that often present with pus.
Strep pyogenes are also called Group A Strep – GAS - in Lancefield classification developed by American microbiologist Rebecca Lancefield.
Ok now, Strep pyogenes has a thick peptidoglycan cell wall, which takes in purple dye when Gram-stained - so this is a gram-positive bacteria.

Bacterial characteristics 0:35–2:30

It’s non-motile and doesn’t form spores, and it’s also a facultative anaerobe, meaning it can survive in both aerobic and anaerobic environments.
Finally, Strep pyogenes is catalase negative, meaning it doesn’t make an enzyme called catalase. However, unlike other common cocci like Enterococci, Strep pyogenes is pyrrolidonyl arylamidase positive, because it makes an enzyme called L-pyrrolidonyl arylamidase.
To test for this, a small sample is taken from a suspected bacterial colony, and then inoculated to a disk pad that’s embedded with pyrrolidonyl beta naphthylamide - another joy of a word.
With Strep pyogenes, pyrrolidonyl arylamidase hydrolyzes pyrrolidonyl beta—naphthylamide to produce beta-naphthylamide. Try saying that 3 times fast!
Finally, another reagent called N-methylamino-cinnamaldehyde is added to the disk, and it reacts with beta—naphthylamide, resulting in a bright red color that confirms Strep pyogenes is pyrrolidonyl arylamidase positive.When cultivated on a medium called blood agar, Strep pyogenes colonies cause beta-hemolysis, also called complete hemolysis.
That’s because Strep pyogenes makes toxins known as streptolysins, which hydrolyze the hemoglobin in red blood cells to transparent yellow color byproducts.
But some other Streptococcus species, like Strep agalactiae, are also beta-hemolytic. So a bacitracin test is done to distinguish Strep pyogenes.
That’s when a disk of bacitracin is added to the blood agar. Strep pyogenes is bacitracin sensitive, so the colonies die off, whereas with Strep agalactiae, the colonies remain intact.

Pathophysiology 2:30–6:39

Now, Strep pyogenes has a number of virulence factors, that are like assault weaponry that help it attack and destroy the host cells, and evade the immune system.
So first, Strep pyogenes is encapsulated, meaning it’s covered by a polysaccharide layer called a capsule. And on the capsule, there are adherence proteins such as lipoteichoic acid, Streptococcus fibronectin binding protein - or Sfbl for short, and M protein, which help Strep pyogenes attach to the host cells, like those in the skin or the pharyngeal mucosa.
Then, Strep pyogenes uses toxins like hyaluronidase, which destroys hyaluronic acid, a cement substance that keeps cells of the connective tissues and blood vessels tightly linked.
Destruction of hyaluronic acid results in local inflammation, and enables the bacteria to spread to the bloodstream. In the bloodstream, Strep pyogenes uses streptolysin O and S, which are toxins that cause hemolysis, or red blood cell destruction.
It also uses erythrogenic toxins, that are also called Streptococcal Pyrogenic Exotoxins, or Spe for short, which come in 3 flavors: SpeA, SpeB, and SpeC.
This leads to increased hemolysis in the dermal and submucosal blood capillaries. What is more, SpeA and SpeC are superantigens, meaning they don’t need to be eaten up and processed by an antigen-presenting cell such as a macrophage to generate an immune response from T-cells.
Instead, they interact immediately with the class II MHC molecule on the surface of the macrophage, forming a superantigen-MHC complex, which then interacts with the T-cell receptor and stimulates up to 30% of the entire T- cell population.
This is 300 times powerful the conventional antigens, and it stimulates the release of a whole bunch of inflammatory cytokines.
Specifically, this is called a cytokine storm, and it can result in toxic shock syndrome or TSS, which happens when a such cytokine storm triggers widespread systemic vasodilation, making blood pressure drop, which leads to poor perfusion of vital organs.From the bloodstream, strep pyogenes bacteria can spread to other organs, like the lungs, causing pneumonia or lung abscesses, or the heart, where they form clumps called vegetations on the heart valves, causing infective endocarditis.
Alternatively, if they spread to central nervous system, they can cause brain abscesses, or meningitis.Surprisingly, despite all that powerful arsenal, Strep pyogenes can actually peacefully colonize the skin, the mucosa of the pharynx or throat, the vagina, and the rectum.
It doesn’t do any harm so long as the immune system keeps them in check, restricting their growth and preventing them from spreading somewhere else in the body.
Problems arise in individuals with weaker immune systems, like infants and the elderly. Other immune-weakening conditions include HIV infection, diabetes, or a malignancy.
In these cases, Strep pyogenes usually gets in the bloodstream through a breach on the skin, a mucosal laceration, or following surgery.
Most often, Strep pyogenes causes strep pharyngitis also called strep throat, which is the inflammation of the pharyngeal mucosa and tonsils.
Strep pharyngitis may also be associated with scarlet fever, which is when intracapillary hemolysis results in a bright-red skin rash.
When Strep pyogenes infects the epidermis, it causes impetigo, which are superficial skin lesions that look like honey clusters.
If the bacteria invades deeper, it can infect the upper dermis and superficial lymphatics, causing another skin infection called erysipelas.
If it gets to the lower dermis, it causes cellulitis, which is an acute, painful, quick-spreading infection of the lower dermis and subcutaneous tissues.

Complications 6:39–8:14

Sometimes, the infection can spread even deeper, to the muscle fascia, causing necrotizing fasciitis, which is when the muscle fascia and subcutaneous tissue are destroyed in a process called necrosis.
Finally, Strep pyogenes can also cause post-infectious sequelae - which are complications that arise even after the bacteria has been eliminated from the body.
For example, following strep pharyngitis, there may be acute rheumatic fever – or ARF for short. This complication arises because Strep pyogenes has a bacterial M protein that Mimics the structure of some proteins which make up some tissues of the body, like the myosin and glycogen of heart muscle and smooth muscle cells.
This is not to say that they’re identical - but rather that they’re similar enough for the immune system to confuse these self structures with the bacterial M protein, resulting in a type II sensitivity reaction.
This means that the immune system releases a whole lot of IgG and IgM antibodies, that are aimed to destroy the bacteria M proteins, but instead attack the heart muscle, causing myocarditis, the heart valves, causing infective endocarditis, or the pericardium, causing pericarditis.
Another post-strep pyogenes complication is post-streptococcal glomerulonephritis - which means acute inflammation of the kidneys’ glomeruli, most commonly seen after impetigo.
It typically occurs two to four weeks after the initial infection, because of a type III sensitivity reaction. This means that the streptococcal antigens that remain in the blood, combine with antibodies and form antigen-antibody complexes that are deposited in the basement membrane of the glomerulus.

Clinical manifestations 8:14–9:34

This can activate the complement system, and attract neutrophils to the glomeruli, resulting in kidney damage. Symptoms depend on the particular infection.
With pharyngitis, there is fever, painful swallowing and the tonsils look reddish, swollen, and there may be pus on them.
With impetigo, there are itchy honey-colored scabs on skin which can become fluid filled blisters. With erysipelas there are warm and painful lesions on the skin, with raised edges.
With necrotizing fasciitis, there’s fever, and the skin over the affected part becomes painful and purple-colored. With scarlet fever, there’s fever, a bright-red skin rash, sometimes the tongue has a sandpaper feel.
Finally, with acute rheumatic fever, there’s a mnemonic for the symptoms - that’s JONES. J is for Joints inflammation, O is for heart damage that causes new heart murmurs, N is for subcutaneous nodules typically seen on the elbows, knees and the forearm.
E is for Erythema marginatum, a rash with thick red margins, and finally, S is for Sydenham’s chorea, which is characterized by rapid involuntary movement of the face and hands.

Diagnosis 9:34–10:49

With post-streptococcal glomerulonephritis, there is mainly facial edema, and dark red urine, because glomerular damage allows red blood cells to pass in the urine.
Diagnosis of strep pharyngitis can be done with rapid strep test, or RST, which looks for bacterial antigens in a throat swab.
However, since this bacteria can peacefully colonize people’s pharynges, RST gives a lot of false positives. So a definitive diagnosis requires a culture from the throat swab.
For skin infections, cultures can be done from the fluid inside blisters or from debrided tissues, and blood cultures can be done when a systemic infection is suspected.
Ultimately, the treatment of Strep pyogenes infections is penicillin, because unlike to some other streptococcal species which have developed penicillin resistance over time, Strep pyogenes is still sensitive to good old penicillin G.
For people who are allergic to penicillin, cephalosporins such as ceftriaxone, and macrolides such as azithromycin may be used.
Additionally, for necrotizing fasciitis, urgent tissue debridement is necessary. ##SummaryAlright, as a quick recap, Streptococcus pyogenes, are gram-positive round bacteria that live in chains.

Review 10:49–11:37

They non-motile, non-spore forming, beta hemolytic, and bacitracin sensitive. They colonize the pharynx, vagina or the skin, where they’re part of the normal flora, but in some cases, they may take advantage of a weakened immune system and causes infections like strep pharyngitis, scarlet fever, impetigo, necrotizing fasciitis.
Post-infectious sequelae include acute rheumatic fever and post-streptococcal glomerulonephritis. Diagnosis may be done with a rapid strep test for throat infections, but a definitive diagnosis requires cultures from the affected site.
Treatment can be done with penicillin G, and alternatives include cephalosporins such as ceftriaxone,