Virulence factors, Pathogenesis and Clinical manifestations of Streptococcus pneumoniae

Virulence factors of Streptococcus pneumoniae

Polysaccharide capsule

• The capsule is antiphagocytic, inhibiting complement deposition and phagocytosis.

2. Cell wall associated polymers and proteins

• Teichoic acid – binds to epithelial cells and activates alternative complement pathway
• Protein adhesion – binds to epithelial cells
• Peptidogylcan – activates alternative complement pathway
• Phosphorylcholine – mediates invasion of host cell
• F protein – mediates attachment to epithelial cells

3. Pneumolysin

• It is intracellular membrane-damaging toxin produced by autolysis.
• Pneumolysin binds to cholesterol and therefore interacts indiscriminately with all cell types.
• This toxin stimulates production of proinflammatory cytokines.
• Pneumolysin inhibits:
  • neutrophil chemotaxis
  • phagocytosis and the respiratory burst
  • lymphocyte proliferation and immunoglobulin synthesis.

4. Pili

• Pili enable the attachment of encapsulated pneumococci to the epithelial cells of the upper respiratory tract.
• However it is not present in all strains.

5. IgA1 protease

• It is extracellular protease that specifically cleaves human IgA1 in the hinge region.
• This protease enables these pathogens to evade the protective functions of the principal immunoglobulin isotype of the upper respiratory tract.

6. Autolysins

• Autolysins are enzymes that hydrolyze the components of a biological cell in which it is produced.
• When activated, the pneumococcal breaks the peptide cross-linking of the cell wall peptidoglycan, leading to lysis of the bacteria.
• Autolysis enables the release of pneumolysin and, in addition, large amounts of cell wall fragments.

Pathogenesis of Streptococcus pneumoniae

• Transmission from a sick person, or more commonly from an asymptomatic carrier, occurs through droplets of respiratory secretions that remain airborne over distances of a few feet.
• Infecting organisms can also be carried on hands contaminated with secretions.
• S. pneumoniae colonizes the oropharynx by adhering to the epithelial cells of pharynx.
• This adhesion is mediated by pneumococcal neuraminidase or by pneumococcal cell-surface ligands of the cocci called adhesins.
• Subsequent migration of the organism to the lower respiratory tract can be prevented if the bacteria are enveloped in mucus and removed from the airways by the action of ciliated epithelial cells.
• The bacteria counteract this envelopment by producing secretory IgA protease and
• The secretory IgA protease destroys the secretory IgA and thereby enhances the ability of the cocci to colonize mucosa of the upper respiratory tract.
• Pneumolysin, on the other hand, destroys the ciliated epithelial cells and phagocytic cells by binding to cholesterol in the epithelial cell membrane.
• This activity can destroy the ciliated epithelial cells and phagocytic cells.
• The process of tissue destruction is mediated by factors, such as cell wall teichoic acid, peptidoglycan, and phosphorylcholine.
• The destructive action is further supplemented by hydrogen peroxide produced by the bacteria caused by reactive oxygen intermediates.
• Teichoic acid and the peptidoglycan fragments activate the alternative complement pathway, producing C5a, which being chemotaxic attracts neutrophils to the site of inflammation and mediates the inflammatory process.
• Migration of inflammatory cells to the site of infection is the key feature of pneumococcal infection.
• In turn, cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), are produced by the activated leukocytes, leading to the further migration of inflammatory cells to the site of infection, fever, tissue damage, and other signs characteristic of pneumococcal infection.
• Finally, phosphorylcholine present in the bacterial cell wall can bind to receptors for platelet-activating factor that are expressed on the surface of endothelial cells, leukocytes, platelets, and tissue cells, such as those in the lungs and meninges.
• By binding these receptors, the bacteria can enter the cells, where they are protected from opsonization and phagocytosis, and pass into sequestered areas, such as blood and the central nervous system.
• This activity facilitates the spread of disease.
• S. pneumoniae survives phagocytosis because of the antiphagocytic protection afforded by its capsule and the pneumolysin-mediated suppression of the phagocytic cell oxidative burst, which is required for intracellular killing.
• Antibodies directed against the type-specific capsular polysaccharides protect against disease caused by immunologically related strains.
• These antibodies appearing in serum 5–8 days after the onset of infection are protective against the pneumococcal serotype causing the infection.
• Humoral factors, including antibodies, complement, and perhaps C reactive protein (CRP), assist macrophages in the spleen, liver, and lymph nodes in carrying out their filtering function.

Clinical manifestations of Streptococcus pneumoniae

A. Pneumonia

• Pneumonia is a leading cause of death, especially in older adults and those whose resistance is impaired and is caused most frequently by S. pneumonia.
• Since the disease is associated with aspiration and is localized in the lower lobes of the lungs, it is called lobar pneumonia.
• However, children and the elderly can have a more generalized bronchopneumonia.
• Pneumococcal pneumonia develops when the bacteria multiply in the alveolar spaces.
• Erythrocytes, leaking from congested capillaries, accumulate in the alveoli, followed by the neutrophils, then the alveolar macrophages.
• The onset of the clinical manifestations of pneumococcal pneumonia is abrupt, consisting of a severe shaking chill and sustained fever of 39° C to 41° C.
• Most patients have a productive cough with blood-tinged sputum, and they commonly have chest pain (pleurisy).
• Occasionally, lung necrosis and intrapulmonary abscess formation occur with the more virulent pneumococcal serotypes.
• Pleural effusions are seen in approximately 25% of patients with pneumococcal pneumonia and empyema (purulent effusion) is a rare complication.

B. Sinusitis and otitis media

• The disease is usually preceded by a viral infection of the upper respiratory tract, after which polymorphonuclear neutrophils (leukocytes) (PMNs) infiltrate and obstruct the sinuses and ear canal.
• The viral infection lowers the mucosal immunity, facilitating the invasion by S. pneumonia.
• Sinusitis caused by the pneumococci occurs in patients of all ages, but middle ear infections (otitis media) caused by the bacteria is seen only in young children.

C. Bacteremia

• In the absence of a focus of infection bacteremia/sepsis is commonly caused by pneumococcus, especially in individuals who are functionally or anatomically asplenic.
• In contrast, bacteria are generally not present in the blood of patients with sinusitis or otitis media.
• Bacteremia from pneumonia has a triad of severe complications: meningitis, endocarditis, and septic arthritis.

D. Meningitis

• S. pneumoniae is among the three leading causes of bacterial meningitis.
• Meningitis is always secondary to other pneumococcal infections, such as pneumonia, bacteremia, infections of the ear or sinuses.
• Pneumococcus is the most common cause of pyogenic meningitis in children, although the condition can occur in all age groups.
• The bacteria reach the brain through blood stream or from nasopharynx (following head trauma or dural tear particularly with cerebrospinal fluid leak).
• Meningitis caused by S. pneumoniae is associated with a higher mortality and more neurological complications than the meningitis caused by any other bacteria.