The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease

Key Points Streptococcus pneumoniae (commonly referred to as the pneumococcus) interacts with numerous host structures during respiratory colonization, and several bacterial adhesins have been identified. These include: phosphorylcholine, which mediates bacterial adherence to the platelet-activating-factor receptor; choline-binding protein A, which binds to human secretory component; neuraminidases, which cleave host glycoconjugates; and hyaluronidase and PavA, which bind to extracellular matrix components. Important components of innate and adaptive immunity during respiratory infection include: neutrophil infiltration, complement, phagocytosis, Toll-like receptor (TLR) 2-dependent inflammation, antibody-independent CD4 + T-cell protection and pneumolysin–TLR4 interactions Major pneumococcal-protein virulence factors, such as pneumolysin, neuraminidases, the cell-surface proteins PspA, PspC and LytA and the metal-ion-binding proteins PsaA, PiaA and PiuA, have specific roles in respiratory colonization and disease. The pneumococcal capsule reduces entrapment in the mucus, which allows the pneumococcus to access epithelial surfaces. Capsules are antiphagocytic, and can reduce the total amount of complement that is deposited on the bacterial surface and the number of pneumococcal cells that are trapped in neutrophil extracellular traps. Most pneumococcal isolates that have been investigated display phase variation between two forms that can be distinguished by their opaque or transparent colony morphologies. Here, these morphologies are reviewed in more detail. The important role of capsule regulation in virulence is also discussed. Streptococcus pneumoniae is one of the most common bacterial respiratory pathogens. In this article, the authors review the impressive armamentarium of virulence factors the pneumococcus uses to colonize the upper and lower respiratory tracts of the host and cause disease. Streptococcus pneumoniae is a Gram-positive bacterial pathogen that colonizes the mucosal surfaces of the host nasopharynx and upper airway. Through a combination of virulence-factor activity and an ability to evade the early components of the host immune response, this organism can spread from the upper respiratory tract to the sterile regions of the lower respiratory tract, which leads to pneumonia. In this Review, we describe how S. pneumoniae uses its armamentarium of virulence factors to colonize the upper and lower respiratory tracts of the host and cause