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  • Review Article
  • Published:

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

Nature Reviews Microbiology volume 6, pages 288–301 (2008)Cite this article

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.

Abstract

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 disease.

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Figure 1: Nasal colonization by Streptococcus pneumoniae.
Figure 2: Pneumococcal virulence factors.
Figure 3: Steps in Streptococcus pneumoniae capsule biosynthesis.
Figure 4: Model showing the regulation of capsular polysaccharide (CPS) production by tyrosine phosphorylation of CpsD.

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Authors and Affiliations

  1. Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, LE1 9HN, United Kingdom

    Aras Kadioglu & Peter W. Andrew

  2. Department of Microbiology, School of Medicine, University of Pennsylvania, Pennsylvania, 19104-6076, USA

    Jeffrey N. Weiser

  3. School of Molecular and Biomedical Science, University of Adelaide, South Australia, 5005, Australia

    James C. Paton

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  1. Aras Kadioglu
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Correspondence to Aras Kadioglu.

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DATABASES

Entrez Genome Project

Actinobacillus actinomycetemcomitans

Haemophilus influenzae

Streptococcus pneumoniae

Entrez Protein

BgaA

CcpA

CpsC

CpsD

CRP

LytA

PiaA

StrH

FURTHER INFORMATION

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Jeffrey N. Weiser's homepage

Glossary

Naso–oropharynx

The parts of the pharynx that are above and below the palate, respectively.

Carrier state

The state of carrying an organism without manifestation of disease.

Herd immunity

Immunity induced by vaccination that protects a proportion of unvaccinated individuals.

Glycocalyx

Extracellular polysaccharide material that is excreted by epithelial cells and forms an outer layer on epithelial surfaces.

Phase variation

A molecular mechanism that leads to switching of the gene-expression state; for example, on–off expression.

Lipoteichoic acid

A teichoic acid species that is connected to membrane glycolipids. The stereochemistry of LTAs and the biosynthetic origin of the glycerolphosphates are different from those of wall teichoic acids, which have glycerol-phosphate backbones.

Human secretory component

An epithelial glycoprotein that is required for the active transport of polymeric immunoglobulins across mucosal surfaces.

Glycoconjugate

A carbohydrate that is covalently linked to other chemical species.

Basement membrane

A tissue structure that consists of a network of collagen fibres that attach the overlying epithelial layer to the connective tissue underneath.

Complement

A part of the innate immune system that comprises serum proteins which can protect against infection.

Fab fragment

The region of an antibody that binds to an antigen.

Bacteriocin

A bacterially produced, small, heat-stable peptide that is active against other bacteria and to which the producer has a specific immunity mechanism. Bacteriocins can have a narrow or broad target spectrum.

Opsonic antibody

A bacteria-binding (opsonizing) antibody, such as IgG and IgA, that interacts with Fc receptors on phagocytic cells, which leads to an increased uptake of bacteria.

Teichoic acid

A cell-envelope glycopolymer that is composed of many identical sugar-phosphate repeating units, which are usually modified with D-alanine and additional sugars.

Apolactoferrin

The iron-depleted form of the glycoprotein lactoferrin.

Factor H

A component of the alternative complement pathway that is involved in the regulation of complement activation.

C-type lectin

A carbohydrate-binding protein that is found in a wide range of animals. C-type lectins share a highly conserved calcium-dependent carbohydrate-recognition domain that is used to distinguish them from other animal lectins.

Clonal type

A pneumococcal clonal lineage is determined by sequence analysis of a set of housekeeping genes, as opposed to its capsular serotype.

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Kadioglu, A., Weiser, J., Paton, J. et al. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Microbiol 6, 288–301 (2008). https://doi.org/10.1038/nrmicro1871

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