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Core
Classification of Streptococci
Streptococci are a genus (a group of closely related species) of Gram-positive cocci that usually assemble linearly forming chains.
Streptococci are classified based on their haemolytic properties:
- (Alpha) α haemolysis: these species have the ability to oxidise iron in haemoglobin molecules (partial haemolysis). This gives the characteristic greenish colour that emanates around them when cultured on a blood agar plate (a dish of jelly-like growth medium, called agar, enriched with blood). Some examples belonging to this group include: Streptococcus pneumoniae (the pneumococcus) and the group of ‘viridans’ (literally green) streptococci.
- (Beta) β haemolysis: these species cause complete breakdown of red blood cells (full haemolysis). This results in the characteristic transparent ‘halo’ surrounding the colonies (visible clumps of bacteria) when cultured on a blood agar plate. An important example is S. pyogenes.
- (Gamma) γ haemolytic species: these species cause no haemolysis and simply appear as normal colonies on a blood agar plate, not creating any discolouration or ‘halo’ around them. One example is Streptococcus gallolyticus (formerly called Streptococcus bovis), a gut bacterium linked to infective endocarditis (infection of the heart valves) and colorectal (bowel) cancer.
Figure: Different haemolytic patterns
Creative commons source by Y tambe, edited by Dr. Elena Perez [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0/)]
There are a few other ways to describe streptococci. One of them is known as Lancefield grouping (the serological method) and is based on cell wall antigens (the specific carbohydrates found on the bacterial cell wall). The groups are lettered A to V (not every letter is used). For example, group B streptococcus (so called because it belongs to Lancefield group B) causes neonatal sepsis (sepsis in newborn babies). Another way of classifying streptococci, known as Sherman’s grouping, is based on their biochemical and physiological properties. It describes whether the streptococcus species is pyogenic (pus-forming), viridans, enterococcal (the enterococci, which normally live in the gut) or lactic (lactic acid-producing). So, for example, S. pyogenes is beta-haemolytic (by its haemolytic pattern), pyogenic (in Sherman’s grouping) and group A (in Lancefield grouping).
Many streptococci are part of our normal flora (the harmless microorganisms that normally live on and in the body). However, disease-causing (pathogenic) species have a number of virulence factors (molecules and mechanisms that increase a bacterium’s effectiveness and ability to multiply). These make it hard for the body to eliminate the infection on its own.
Let’s look at Streptococcus pyogenes as an example: some of its virulence factors found in group A streptococci include:
- M protein which helps the bacteria resist destruction by the immune system. It does this by inhibiting activation of the alternative complement pathway (complement is a set of blood proteins that help the immune system destroy bacteria). It also promotes initial attachment;
- A large hyaluronic acid capsule (a protective outer coat) that prevents recognition and phagocytosis by macrophages and neutrophils (as it mimics the hyaluronic acid found in human connective tissue);
- Pyrogenic exotoxins (fever-causing toxins released by the bacteria) that act as superantigens. Superantigens switch on very large numbers of T cells (a type of immune cell) at once. This triggers widespread T cell activation and cytokine release (cytokines are chemical signals between immune cells);
- Streptokinase which dissolves clots by converting plasminogen (an inactive blood protein) into plasmin (the enzyme that breaks down clots), helping the bacteria to spread;
- Streptolysins O and S that cause lysis (bursting) of the host’s erythrocytes (red blood cells), neutrophils and platelets;
- DNAses A, B, C and D (enzymes) that break down DNA, which helps the bacteria escape from neutrophil extracellular traps (nets of DNA that neutrophils release to trap microbes).
Note that not all S. pyogenes strains (genetically distinct versions of the species) carry all of these virulence factors.
Diseases caused by S. pyogenes infections
One of the clinical manifestations of a S. pyogenes infection is streptococcal pharyngitis (inflammation of the throat), commonly referred to as strep throat. It mainly affects school-aged children and teenagers, and is transmitted via droplet spread. Most sore throats are caused by viruses, and group A streptococcus accounts for less than a third of cases of acute pharyngitis. Streptococcal pharyngitis starts as a sore throat, later with malaise (feeling generally unwell), fever and headache. The tonsils then swell and may take on a characteristic pustular (pus-spotted) appearance. The management of streptococcal pharyngitis is guided by clinical assessment and, where appropriate, microbiological testing. Most people get better within about a week with or without antibiotics. NICE (the National Institute for Health and Care Excellence) therefore advises using the FeverPAIN or Centor score (scoring systems based on symptoms and signs) to identify who is most likely to benefit. Antibiotics are not offered for a low score. For a high score (a high likelihood of group A streptococcal infection), an immediate or back-up antibiotic prescription (one to be used only if symptoms do not improve) is considered, because antibiotics reduce the risk of complications such as acute rheumatic fever, shorten symptoms slightly (by about 16 hours on average) and limit transmission. The benefit to any one person is small, and acute rheumatic fever is now very rare in the UK. The first-choice antibiotic is phenoxymethylpenicillin (penicillin V, an oral penicillin). Supportive treatment is also important for symptom control. In times of increasing antibiotic resistance (see our article on antibiotics), antibiotics should only be prescribed when they are likely to help. Some strains also produce pyrogenic exotoxins (fever-causing toxins). Infection with these strains can cause scarlet fever: a characteristic rash on top of the symptoms above, caused by the erythrogenic (rash-producing) action of the toxins. Scarlet fever needs prompt antibiotic treatment (in the UK, a 10-day course of phenoxymethylpenicillin is the first choice), and suspected cases are notified to the local health protection team. People with severe suppurative complications (see below) are referred to hospital.
Figure: Typical rash seen in scarlet fever
Public Domain Source Internet [Archive Book Images [No restrictions]]
Other complications that can arise from streptococcal pharyngitis are:
- Suppurative complications (pus-forming): for example peritonsillar abscesses (collections of pus beside the tonsil, also called quinsy) and retropharyngeal abscesses (behind the back of the throat). Retropharyngeal abscesses in particular can spread to the mediastinum (the central part of the chest between the lungs), causing a severe deep tissue infection with high mortality.
- Acute rheumatic fever: an immune-mediated complication that can follow group A streptococcal infection of the throat. Skin infection may also trigger it, but the evidence for this is less certain. The bacteria do not damage the tissues directly. Instead, the immune response to them is thought to attack the body’s own tissues. This may happen through cross-reactivity (molecular mimicry: the immune response to M protein also recognises similar-looking human heart proteins) or through binding of M protein to the host’s collagen. Some people may also be genetically predisposed. Symptoms typically appear about 2 to 4 weeks after the initial infection (1 to 5 weeks in some people). They can affect different parts of the body, including the heart, brain (jerky, uncontrollable movements called chorea), joints and skin.
- Acute post-streptococcal glomerulonephritis: an acute inflammation of the renal glomerulus caused by deposition of antigen-antibody complexes in the glomeruli.
Some important skin infections that S. pyogenes can cause (impetigo and cellulitis can also be caused by Staphylococcus aureus):
- Impetigo: usually affects children between the ages of 2 and 5 and is characterised by honey-coloured crusted lesions (sores). The pathogenesis (how the disease develops) starts with skin colonisation (bacteria settling on the skin surface), followed by intradermal inoculation (the bacteria getting into the skin through a break). Without treatment, impetigo usually heals by itself in 7 to 21 days, although treatment can speed recovery and limit spread. Post-streptococcal glomerulonephritis (inflammation of the kidney’s filtering units) is an uncommon complication.
- Erysipelas: a superficial skin infection most commonly found on the face and lower limbs. It usually follows a break in the skin, and causes a rapidly developing hot, red and swollen lesion with a well-defined, raised edge.
- Cellulitis: a deeper infection of the skin and subcutaneous tissue. Bacteria usually enter through a break in the skin. It is caused by streptococci and Staphylococcus species, including S. aureus.
- Necrotising fasciitis: an infection of the deep tissues and fascia (the sheets of connective tissue around muscles) that leads to rapid necrosis. Symptoms usually include severe pain out of proportion to visible signs, often before obvious skin changes, followed by systemic features such as fever. This is a medical emergency with high mortality. It requires urgent surgical debridement (cutting away dead tissue) and prompt IV antibiotics. These are typically broad-spectrum regimens (active against many types of bacteria) that include an antibiotic that also suppresses toxin production. Further surgery, including amputation, may be required. Diagnosis is ultimately surgical, with findings of extensive tissue destruction.
Figure: Impetigo
Creative commons source by Pp96 [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Figure: Erysipelas
Creative commons source by Klaus D. Peter, Gummersbach, Germany [CC BY 3.0 de (https://creativecommons.org/licenses/by/3.0/de/deed.en)]
Figure: Cellulitis
Public Domain Image Source https://www.flickr.com/photos/104346167@N06/44699140442
Figure: Necrotising Fasciitis. Note the characteristic blood blisters and widespread damage
Creative commons source by Piotr Smuszkiewicz, Iwona Trojanowska and Hanna Tomczak [CC BY 3.0 de (https://creativecommons.org/licenses/by/3.0/de/deed.en)]
Finally, toxic shock syndrome (TSS) is a very serious reaction to exotoxins (toxins released by bacteria). It can be caused by S. pyogenes (streptococcal TSS) or by Staphylococcus aureus, including meticillin-resistant Staphylococcus aureus (MRSA). Streptococcal TSS is typically associated with invasive infection (infection that has spread into the deep tissues or blood). It can quickly progress to bacteraemia (bacteria in the blood), vascular collapse and ultimately organ failure if not recognised early. Staphylococcal TSS can also follow tampon or menstrual cup use or an infected wound. Patients can deteriorate rapidly over hours. The shock is caused by exotoxins that act as superantigens, triggering widespread T cell activation and a non-specific inflammatory response throughout the body, leading to vascular collapse.
Edited by: Dr. Ben Appleby and Dr. Marcus Judge
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