Streptococcus: Genus, Classification, and Properties

• Streptococcus is a genus of gram-positive, spherical bacteria (cocci) belonging to the family Streptococcaceae.
• These bacteria tend to form pairs or chains.
• The name Streptococcus comes from the Greek word "strepto" (pliant) and the Latin word "coccus" (grain, seed).
• Some Streptococcus members are human pathogens, while others are part of the normal flora of the oropharynx and gastrointestinal tract.

Scientific Classification

• Domain: Bacteria
• Phylum: Bacillota
• Class: Bacilli
• Order: Lactobacillales
• Family: Streptococcaceae
• Genus: Streptococcus
• Species: Over 100

Properties

• Gram-positive and spherical (cocci).
• Arranged in pairs or chains.
• Catalase-negative.
• Important human pathogens include Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, Viridans streptococci, and Streptococcus pneumoniae.
• Hemolysis type is an important characteristic for identification.

Hemolysis Types

• Alpha-hemolytic: Forms a green zone around colonies due to partial lysis of red blood cells.
• Beta-hemolytic: Forms a clear zone around colonies due to complete lysis of red blood cells.
• Gamma-hemolytic: Unable to hemolyze red blood cells (non-hemolytic).
• Lancefield antigens were historically used to differentiate streptococci, but are now less relied upon because of the large variety of Streptococci.
• Identification now uses a combination of tests, including hemolysis, antigenic combinations, biochemical reactions, growth characteristics, and genetic studies.

Beta-Hemolytic Streptococci

• Arranged into Lancefield groups A-U.
• Group determined by precipitation tests with antisera or by immunofluorescence.
• Group A (Streptococcus pyogenes):
  • The most important human pathogen.
  • Many strains have a hyaluronic acid capsule that is anti-phagocytic.
  • Causes pharyngitis and skin infections.
• Group B (S. agalactiae):
  • Colonizes the genital tract of some women and can cause neonatal meningitis and sepsis.
  • Usually bacitracin-resistant.
  • Hydrolyzes hippurate, an important diagnostic criterion.
• Group D (Enterococcus, e.g., Enterococcus faecalis and Enterococcus faecium):
  • Members of the normal flora of the colon.
  • Cause urinary and cardiovascular infections.
  • Very hardy, not easily killed by penicillin G.
• Non-enterococcus group D (S. bovis):
  • Can cause similar infections but are less hardy.
  • Inhibited by 6.5% NaCl and killed by penicillin G.
• Groups C, E, F, G, H, and K-U: Infrequently cause human diseases.

Non-Beta-Hemolytic Streptococci

• Some are non-hemolytic, while others produce alpha-hemolysis.
• Principle organisms: S. pneumoniae and the viridans group of streptococci.
• S. pneumoniae are bile-soluble and inhibited by optochin, differentiating them from S. viridans.
• S. pneumoniae is optochin-sensitive, showing a zone of inhibition (>14mm) around the optochin disk, while S. viridans is resistant and grows without inhibition.

Transmission

• Most streptococci are part of the normal flora of the human throat, skin, and intestines but can cause disease if they gain access to tissues or blood.
• Viridans streptococci and S. pneumoniae are mainly found in the oropharynx.
• S. pyogenes is found on the skin and in the oropharynx in small numbers.
• S. agalactiae occurs in the female genital tract.
• Enterococci and anaerobic streptococci are found in the lower intestinal tract.

Pathogenesis

• Group A streptococci cause diseases through three mechanisms:
  • Pyogenic inflammation: Local inflammation at the site of the organism in tissue.
  • Exotoxin production: Causes widespread systemic symptoms.
  • Immunological: Antibodies against a component of the organism cross-react with normal tissue or form immune complexes.
• Immunologic reactions cause inflammation, e.g., inflamed joints in rheumatic fever.

Pathogenesis Continued

• Group A streptococci produce important inflammation-related enzymes:
  • Hyaluronidase: degrades hyaluronic acid which is the ground substance of subcutaneous tissue; known as spreading factor.
  • Streptokinase (fibrinolysin): activates plasminogen to form plasmin, which dissolves fibrin in clots, thrombi, and emboli.
  • DNase (streptodornase): depolymerizes DNA in exudates or necrotic tissue.
• Other toxins and hemolysins produced by Group A streptococci:
  • Erythrogenic toxin: Causes the rash of scarlet fever.
  • Streptolysin O: Hemolysin.
  • Streptolysin S: Hemolysin.
  • Pyrogenic exotoxin: Causes shock syndrome.
  • Exotoxin B: Degrades host serum.

Virulence Factors - GAS

• Capsule: Anti-phagocytic and allows specific attachment to tissues.
• M-protein in cell wall: Anti-phagocytic and allows specific attachment to tissues.
• Streptolysin O and S: Leukocidins against neutrophils and macrophages.
• Streptococcal pyrogenic exotoxins (SPEs): "Superantigens" that directly stimulate T-cells, causing them to release high levels of cytokines, leading to fever and shock.

Virulence Factors – GAS cont…

• Pyrogenic exotoxin (SPE): Responsible for tissue destruction, including skin lesions and potentially scarlet fever.
• Hyaluronidase: Dissolves hyaluronic acid that holds cellular basement membranes together (a "spreading factor").

Clinical Findings

• S. pyogenes (Group A Streptococcus) is the most common bacterial cause of sore throat.
• Pharyngitis: Characterized by inflammation, exudate, fever, leucocytosis, and tender cervical lymph nodes.

Complications

• Untreated, spontaneous recovery occurs in about 10 days.
• However, complications can include otitis, sinusitis, and meningitis.
• Scarlet fever: Occurs if the infecting streptococci produce erythrogenic toxin and the host lacks antitoxin.
• Rheumatic fever: May occur following pharyngitis.
• Cellulitis, erysipelas, lymphangitis, or bacteremia: Can occur if GAS enters skin defects.
• Endometritis and sepsis (puerperal fever): Can occur if GAS enters the uterus after delivery.
• Streptococcal pyoderma (impetigo): A superficial infection of abraded skin that forms pus or crusts, especially in hot, humid climates.
• Glomerulonephritis: May occur following skin infections.
• Infective endocarditis: Commonly caused by viridans streptococci, which intermittently enter the bloodstream from the oropharynx due to poor dentition or dental surgery; signs include anemia, fever, heart murmur, and embolic events.

Post-Streptococcal Diseases

• Disorders in which a local infection with group A streptococci is followed weeks later by inflammation in an organ not infected by streptococci.

Acute Glomerulonephritis

• Occurs 2-3 weeks after skin infection by certain Group A streptococcal species.
• In children, clinical features include edema of the face, ankles, and smoky urine (due to red cells).
• Most patients recover completely.
• Re-infection with streptococci rarely leads to a recurrence.
• Disease is initiated by antigen-antibody complexes in the glomerular basement membrane, with soluble antigens from streptococcal membranes potentially acting as the inciting antigen.
• Can be prevented by early eradication of nephritogenic streptococci but not by penicillin after onset of symptoms.

Rheumatic Fever

• Occurs 1-4 weeks after any type of Group A streptococcal infection, usually pharyngitis.
• Characterized by fever, migratory polyarthritis, and carditis.
• Carditis causes myocardial and valve damage.
• Due to an immunologic reaction (autoimmune disease).
• Preventable if streptococcal infection is treated within 8 days of onset.
• After a heart-damaging attack of rheumatic fever, re-infection must be prevented by long-term prophylaxis.

Lab Diagnosis

• Stained smear from skin lesions or wounds that reveal streptococci can be diagnostic.
• Culture of swabs from the pharynx.
• Serological diagnosis: ASO titers are high soon after Group A streptococcal infections.

Treatment and Prevention

• All Group A streptococci are susceptible to penicillin G, but neither rheumatic fever nor AGN patients benefit from penicillin treatment after onset.
• Endocarditis caused by most viridans streptococci is curable by prolonged penicillin treatment.
• Prevention of rheumatic fever involves prompt treatment of Group A streptococcal pharyngitis with penicillin.

Streptococcus Pneumoniae

• Pneumococci cause pneumonia, bacteremia, meningitis, and infections of the upper respiratory tract, such as otitis and sinusitis.

Properties

• Spherical cocci arranged in pairs (diplococci) or short chains.
• Possess a polysaccharide capsule, which is a significant virulence factor.

Transmission

• Pneumococci are not highly communicable; 5-50% of healthy individuals carry virulent organisms in the oropharynx.
• Resistance is higher in healthy young people, with disease often resulting in the presence of predisposing factors.

Predisposing Factors

• Alcohol or drug intoxication impairing the cough reflex.
• Abnormalities of the respiratory tract (e.g., viral infection).
• Pooling of mucus, bronchial obstruction, and respiratory tract injury.
• Abnormal circulatory dynamics (e.g., pulmonary congestion and heart failure).
• Chronic diseases (e.g., sickle cell anemia, hyposplenism, malnutrition, and nephrosis).

Pathogenesis

• Pneumolysin: Anti-phagocytic; interferes with the action of tracheal cilia.
• IgA protease: Enhances the organism's ability to colonize the mucosa of the upper respiratory tract.
• Pneumococci multiply in tissue and cause inflammation, leading to the outpouring of fluid and red and white blood cells in the alveoli, resulting in consolidation of the lung.

Clinical Findings

• Pneumonia begins with sudden chills, fever, cough, and pleuritic pain.
• Sputum is red or brown ("rusty" color).
• Bacteremia occurs in 15-25% of cases.
• Spontaneous recovery may begin in 5-10 days, accompanied by the development of anticapsular antibodies.
• Prominent cause of otitis media, sinusitis, purulent bronchitis, and bacterial meningitis.

Lab Diagnosis

• On blood agar, pneumococci form small alpha-hemolytic colonies.
• Colonies are bile-soluble, and growth is inhibited by optochin.

Treatment

• Most pneumococci are susceptible to penicillin and erythromycin.
• People at risk: The Elderly (>65), immunocompromised, and debilitated individuals.
• Ampicillin was previously the drug of choice for enterococcal UTIs and non-urinary infections, but resistance is increasing

Prevention

• Immunization with a polyvalent 23-type polysaccharide vaccine.
• Oral penicillin is given to young children with hypogammaglobulinemia or splenectomy because they respond poorly to the vaccine and are prone to pneumococcal infections.

Group B Streptococcal Disease

• S. agalactiae type III causes neonatal meningitis, and type Ia causes neonatal pneumonia.
• Immunity is induced by antibodies against type-specific antigens.
• Transplacental passage of maternal antibodies protects the neonate against meningitis.

Group D Streptococcus

• Includes S. faecalis and S. faecium (enterococci).
• Common inhabitants of the human gastrointestinal tract and are opportunistic invaders of damaged tissue.
• Cause urinary tract infections, particularly in debilitated or immunosuppressed patients.

Viridans Streptococci

• Includes S. salivarius, S. sanguis, S. mitis, and S. mutans.
• Two major types of human disease are caused by viridans streptococci:
  • Dental caries: Associated with S. mutans, S. salivarius, S. sanguis, and S. mitis.
  • Mutans appears to be the most virulent species; its pathogenicity is due to its ability to adhere to tooth surfaces.
    • Produces large amounts of dextran from sucrose, resulting in plaque formation.
    • Adherent bacteria produce acid fermentation products that dissolve tooth enamel.
  • Bacterial endocarditis: Results from the ability of most viridans streptococci to adhere to human heart valves; the leading cause of bacterial native-valve and prosthetic-valve endocarditis.

Blood Agar

• Sheep's blood agar has advantages over other animal blood:
  • Haemophilus species will not grow on sheep's blood agar.
  • Sheep's blood gives a distinctly clear beta hemolysis compared to other animal bloods
  • Human blood can contain growth-inhibiting antibodies.