Pneumolysin is a protein toxin produced by the bacterium Streptococcus pneumoniae, also known as pneumococcus. It plays a significant role in the bacterium’s ability to cause disease, affecting host cells and immune responses.
The Source and Structure of Pneumolysin
Pneumolysin originates from Streptococcus pneumoniae, a common bacterium responsible for respiratory infections. It is a cholesterol-dependent cytolysin (CDC), a protein toxin produced by Gram-positive bacteria that acts via cholesterol.
Pneumolysin exists as a single, water-soluble molecule, or monomer, within the bacterial cytoplasm. It lacks a typical secretion signal, releasing into the host environment when the bacterial cell undergoes lysis, naturally or due to antibiotic treatment. Its structure changes significantly upon encountering host cells, which is key to its damaging action.
Mechanism of Cellular Attack
Pneumolysin binds to cholesterol, a component found in animal cell membranes. This binding allows the toxin to recognize and adhere to host cell surfaces. The binding of a single pneumolysin molecule then triggers the recruitment of other pneumolysin monomers.
These individual toxin molecules then assemble on the cell surface, forming a large, ring-like prepore complex. This assembly, typically 34 to 50 monomers, creates a structure on the host cell membrane. Once formed, it undergoes a conformational change.
The assembled ring then inserts itself into the cell membrane, creating a large channel or pore. This process involves a vertical collapse of the complex and the insertion of beta-hairpin structures from each monomer into the lipid bilayer. The formation of these pores, which can be around 260 Angstroms (26 nanometers) in diameter, disrupts the cell’s natural barrier. This disruption allows water and ions to flow into the cell, leading to swelling and causing the cell to burst, a process known as lysis.
Sabotaging the Immune Response
The cellular damage inflicted by pneumolysin extends to various components of the body’s defense system. In the airways, pneumolysin can damage ciliated epithelial cells. These cells have cilia that sweep away mucus and trapped pathogens, but their paralysis by the toxin hinders this clearance mechanism, allowing bacteria to establish infections.
Pneumolysin also directly targets and kills immune cells, including macrophages and neutrophils. Macrophages and neutrophils, types of white blood cells, are among the body’s first responders, tasked with engulfing and destroying invading bacteria. By eliminating these cells, the toxin significantly weakens the host’s immediate defense capabilities.
Even at concentrations too low to cause immediate cell bursting, pneumolysin can trigger a strong inflammatory response. This response, while intended to fight infection, can lead to substantial tissue damage in the lungs, contributing to fluid accumulation and impaired lung function. The toxin can activate pathways that release pro-inflammatory signaling molecules, exacerbating inflammation.
Contribution to Disease Development
The localized cellular damage and immune evasion facilitated by pneumolysin contribute directly to the manifestation of specific diseases. In pneumonia, the destruction of lung cells, the paralysis of cilia, and the excessive inflammation induced by pneumolysin collectively lead to the characteristic symptoms. This includes fluid buildup in the lungs and difficulty breathing, as the lung tissue becomes compromised and less efficient at gas exchange.
Pneumolysin also plays a role in the progression to more severe systemic infections, such as bacteremia and sepsis. By forming pores in the endothelial cells that line blood vessels, the toxin helps Streptococcus pneumoniae escape from the lungs and enter the bloodstream. This bacterial presence in the blood (bacteremia) can then trigger a widespread, life-threatening immune reaction throughout the body, known as sepsis.
The toxin further assists in the development of meningitis, a severe infection of the membranes surrounding the brain and spinal cord. Pneumolysin can help the bacteria to cross the blood-brain barrier, a highly selective filter that normally protects the central nervous system. Once across this barrier, the bacteria can infect the meninges, leading to inflammation and the serious clinical outcomes associated with meningitis.