Streptococcus Pyogenes (Student Notes)

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Streptococcus pyogenes is a gram positive cocci that is responsible for several  bacterial infections worldwide. With the aid of its virulence factors, it is able to colonise the human body and cause infections ranging from mild pharyngitits and sinusitis to potentially life threatening necrotizing fasciitis.

In addition to the infections, the antibodies produced to fight it can result in post-streptococcal autoimmune reactions which can result in both heart and kidney failure. Luckily, Streptococcus pyogenes is susceptible to penicillin, which makes most infections relatively easy to treat

Laboratory features

Streptococcus pyogenes are gram-positive cocci that can be seen as blue/purple cocci under the microscope with gram staining. Here they tend to aggregate in long chains. 

Their cultivation is more demanding than for staphylococci as streptococci require vitamin B in the medium. This can be provided by blood agar, on which the streptococci are easily cultivated and show characteristic b-hemolysis around the colonies.

All streptococci species are catalase-negative, this enables us to distinguish them from the various staphylococcus species. This is also true for Streptococcus pyogenes, and the catalase test can be used to differentiate it from staphylococcus aureus, as both show β-hemolysis on blood agar.

Virulence factors

Streptococcus pyogenes possess various virulence factors. Some are associated with their cell membranes, such as adhesion molecules and their outer capsule. They also release exotoxins, exoenzymes and express some membrane-bound enzymes

The virulence factors associated with the cell membrane include lipoteichoic acid found in the cell walls as well as the F-protein. Both facilitate adhesion to host cells. In addition, it has an outer hyaluronic acid capsule that protects it from phagocytosis by host immune cells.

The exotoxins released by Streptococcus pyogenes includes erythrogenic toxin, which causes scarlet fever. Some can also release streptococcal pyogenic exotoxins which are responsible for the rash associated with scarlet fever. 

These toxins can be superantigens which can result in streptococcal toxic shock syndrome. This is an acute, serious, infection characterized by sudden onset of fever and other febrile symptoms.

The exotoxins, streptolysin S and O are also released and can cause various symptoms in infected individuals (more later). In addition, streptolysin O functions as a hemolysin and is responsible for the b-hemolytic activity of the bacteria.

The exoenzymes released by Streptococcus pyogenes include hyaluronidase and streptokinase. Both can serve as invasins, helping the spread of the bacteria.

Hyaluronidase will degrade hyaluronic acid, which is extensive throughout the extracellular matrix (connective tissue). Streptokinase cleaves plasminogen to plasmin, which is the active form of the enzyme which is responsible for fibrinolysis.

The activation of plasminogen to plasmin can cause the breakdown of fibrin which is often deposited at sites of infection/inflammation in order to limit the spread of the inflammation.

Finally, Streptococcus pyogenes can also release DNase which can break down the DNA of the host cells.

Diseases/infections

SP is responsible for a number of diseases in humans which can be grouped into 3 overlapping categories, depending on the severity, and/or spread of the infection. These categories are purulent infections, toxin-mediated infections, and post-streptococcal complications.

Purulent infections

The purulent infections are caused by the bacterias themselves which can gain access to the tissues through the skin or mucosal lesions. The bacteria can be contracted from contact with infected patients or from asymptomatic carriers (~10% of the population) through respiratory droplets, as the bacterium is usually carried in the nasopharynx.

The purulent infections most frequently affect local skin areas or the throat where they cause local infections such as tonsillitis follicularis, pharyngitis (known as strep throat), sinusitis, and impetigo.

If the superficial purulent Streptococcal infections are allowed to spread, it can cause severe conditions such as meningitis and pneumonia, usually after the spread of the bacterium to the bloodstream (bacteremia), as well as deeper skin infections such as erysipelas and necrotizing fasciitis.

Toxin mediated

If the strain is a toxin-producing strain, people can develop toxin-mediated diseases due to Streptococcus pyogenes.

The most frequent disease associated with toxin production is scarlet fever, caused by the release of the erythrogenic toxin. Once released, it can destroy the endothelial cells in capillaries, resulting in red skin rashes. In addition, it induces hypertrophy of the papillae on the tongue, causing them to swell and become red, known as strawberry tongue.

Scarlet fever most frequently affects children after contracting a Streptococcus pyogenes mediated tonsillitis or pharyngitis.

As mentioned, the toxins can also cause streptococcal toxic shock syndrome. This is a severe, rapidly developing infection that after the initial symptoms of fever, muscle pain, and fatigue can result in a septic state with dropping blood pressure and eventually multi-organ failure. 

Risk factors include the use of very absorbent tampons for women. Also, Streptococcus pyogenes and its toxins are one of the causative agents of puerperal fever/sepsis. This is an acute infection that can be contracted by women during, or shortly after delivery.

Post-streptococcal diseases

The post-streptococcal diseases are not infections, but rather complications following infections by Streptococcus pyogenes. This includes anything from streptococcal tonsillitis, pharyngitis to scarlet fever. 

After the infection has been dealt with by the immune system and/or with the aid of antibiotics, the body still has circulating antibodies and immunocomplexes against the bacterial antigens (e.g. M protein). 

Because the bacteria have been killed, they cannot find any antigens to bind to, however, they are able to bind to or deposit in certain tissues. This, in turn, can cause hypersensitive immune reactions, resulting in the immune system attacking the body’s own tissue.

One of these complications is called rheumatic fever, which is a type 2 hypersensitivity reaction. The affected tissues are usually in the joints and heart, as circulating antibodies are able to bind to antigens here. 

This is called cross-reactivity and occurs as some molecular structures on given cells resemble that of the antigens on the bacterial surface. The resulting immune reaction results in inflammation of the endocardium and joints, known as endocarditis and arthritis. It can also affect the skin and brain.

The endocarditis can result in damage to the heart valves over time, resulting in a stiff valve that won’t open sufficiently to allow blood to rush through. This is known as aortic stenosis and can result in heart failure over time.

Arthritis results in a stiff, inflamed, and painful joint. The condition is named rheumatic fever because the symptoms are very similar to those seen in patients with rheumatism. It often develops 2-3 weeks after the initial bacterial infection

Another complication is the type 3 hypersensitivity reactions. In this case, the immunocomplexes formed during the infection are deposited in the joints or on the basal membrane of the kidney glomeruli. In both cases, immune cells are recruited to clear the complexes resulting in inflammation.

In the joints, the inflammation causes a condition known as polyarthritis, which is pain and swelling in more than 5 joints simultaneously. In the glomeruli, the t inflammatory reaction can cause acute glomerulonephritis, in which the kidney filtration membrane can be damaged, resulting in leakage of plasma proteins, etc.

Leakage of plasma proteins such as albumin can lead to hypoalbuminemia which often causes edema to develop. Other possible complications of acute glomerulonephritis include renal failure and hypertensive encephalopathy

The damage caused by the inflammation develops due to activation of the complement system, and both conditions can develop as soon as 1 week after the initial SP infection.

Because there are so many different serotypes of SP, humans can contract SP infections several times during their lifetime. Luckily, scarlet fever is only contracted once, as the erythrogenic toxin has the same structure in all strains. This enables the immune system to generate memory cells, providing immunity towards the toxin in case of repeated infection

Treatment

Luckily, Streptococcus pyogenes is susceptible to penicillin, which makes infections relatively easy to treat, compared to staphylococcal infections. The only complication appears if the patient has a penicillin allergy. In these cases, clindamycin or macrolides such as erythromycin or is used instead.

Following treatment of Streptococcal infections, the development of post-streptococcal complications should be prevented by thorough follow-up on the patient, and/or prolonged administration of prophylactic antibiotics.