Streptococcus Pneumoniae Virulence Factors

Streptococcus pneumoniae (pneumococcus) is one of the most common causes of pneumonia, septicemia, and meningitis in children and adults both in developing and developed countries. S. pneumoniae is the most common causative agent in community-acquired pneumonia (CAP). It produces several virulence factors including polysaccharide capsules, toxin pneumolysin, and enzyme IgA protease that are involved in the disease process.

Autolysin (peptidoglycan hydrolase)

Autolysin is a cell wall degrading enzyme that has the ability to enzymatically disrupt and disintegrate S. pneumoniae. The main autolysin in the pneumococcus is N-acetyl-muramoyl-1-alanine amidase, commonly known as Lyt A. It is thought that when Lyt A is activated the pneumococcal virulence factors such as pneumolysins are released. Autolysin is responsible to kill the entire culture of S. pneumoniae during its stationary phase. Autolysis usually begins within 18-24 hours of culture with colonies collapsing in the centers.

Schematic diagram of the virulence factors of Streptococcus pneumoniae

IgA1 protease

Immunoglobulin A1 (IgA1) is the predominant immunoglobulin isotype involved in the protection of mucosal membranes of the upper respiratory tract in humans. IgA1 proteases of S. pneumoniae cleaves, thus facilitating colonization and invasion on those surfaces. It is an extracellular bacterial enzyme that specifically cleaves human IgA1 in the hinge region at one of the several postproline peptide bonds (absent in the IgA2 molecule).

A number of other human pathogens such as Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhea, and Ureaplasma urealyticum infect and invade mucosal membranes and also have IgA1 cleaving activity.

Pneumolysin (PLY)

Pneumolysin is a pore-forming toxin of 53 kDa composed of 471 amino acids produced by virtually all clinical isolates of the pneumococcus. At high concentration (above 50 hemolytic units), it lyses all cells having cholesterol (receptor for this toxin) on its surface e.g. it damages respiratory epithelium.

Pneumolysin also may cause a range of effects, including induction of apoptosis, activation of host complement, and induce pro-inflammatory reactions in immune cells.

Polysaccharide capsule

Polysaccharide capsule completely encloses the cell of Streptococcus pneumoniae and serves as one of the major virulence factors (probably the most important virulence factor). The importance of the S. pneumoniae capsule for virulence is demonstrated by these facts:

  • all clinical isolates of S. pneumoniae causing invasive disease are encapsulated;
  • loss of the capsule by either genetic mutation or enzymatic degradation dramatically reduces S. pneumoniae virulence in animal models of infection
  • different capsular serotypes vary in the ability to cause invasive disease

The capsule may inhibit complement activity (capsule impaired bacterial opsonization with C3b/iC3b by both the alternative and classical complement pathways and also inhibited conversion of C3b bound to the bacterial surface to iC3b) and phagocytosis.  The capsule also prevents mechanical removal by mucus and reduce exposure to antibiotics

For S. pneumoniae strains, there are >93 antigenically distinct capsular serotypes and antibody to the polysaccharide capsule provides type-specific immunity.

Teichoic acids

Pneumococcal wall teichoic acid is involved in pneumococcal infection of sepsis and adherence to epithelial and endothelial cells. Pneumococcal wall teichoic acid enhances pneumococcal colonization and dissemination.

Other virulence factors of S.pneumoniae includes pneumococcal surface protein A (PspA); protection against the complement system, neuraminidase; (which may enhance colonization due to its action on glycans), and pneumococcal surface antigen A, etc.

References and Further Reading

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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