Streptococcus pneumoniae: transmission, colonization and invasion

Abstract

Streptococcus pneumoniae has a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.

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Fig. 1: The life cycle of Streptococcus pneumoniae and the pathogenesis of pneumococcal disease.
Fig. 2: Bacterial and host factors affecting pneumococcal shedding from carriers.
Fig. 3: Molecular mechanisms of pneumococcal colonization of host surfaces.
Fig. 4: Stages in pneumococcal adherence and invasion.

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Acknowledgements

The authors thank J. Pagano for editorial assistance. J.N.W. is funded by grants from the United States Public Health Service (AI038446 and AI105168). Research in J.C.P.’s laboratory is supported by program grant 1071659 from the National Health and Medical Research Council of Australia (NHMRC); J.C.P. is an NHMRC Senior Principal Research Fellow. D.M.F. is supported by the Medical Research Council (grant MR/M011569/1) and the Bill and Melinda Gates Foundation (grant OPP1117728).

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Nature Reviews Microbiology thanks Sven Hammerschmidt and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Glossary

Upper respiratory tract

(URT). Includes the nasal cavity, paranasal sinuses, mouth, pharynx and larynx and forms the major passages above the trachea.

Community-acquired pneumonia

Infection of the lung acquired outside of hospitals or nursing facilities.

Natural competence

The endogenous ability of a bacterium to alter its genes by taking up extracellular DNA from its environment through transformation.

PolyIC

Polyinosinic:polycytidylic acid is an agonist of Toll-like receptor 3 and mimics double-stranded RNA found in some viruses.

Dexamethasone

An anti-inflammatory corticosteroid.

Fc fragment

The tail region of an antibody that interacts with cell surface receptors and some proteins of the complement system.

Agglutinating function

The clumping of antigens through multivalent binding by antibodies.

Mucociliary flow

A non-immunological defence mechanism that involves ciliary action and the flow of mucus; it clears the respiratory tract of pathogens and particles.

Lectin domains

The carbohydrate-binding domains on proteins.

Bacteriocins

The proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacteria.

Type 1 interferons

A group of signalling proteins expressed and released by host cells to regulate immune responses to pathogens.

Signature-tagged mutagenesis

A genetic technique using DNA signature tags (molecular barcodes) to identify mutants in mixed populations.

Two-component response regulator

The transcription factor component of a stimulus-response mechanism for bacteria to sense and respond to environmental changes.

Quorum sensing

(QS). A system of stimuli and responses that is correlated to microbial population density.

Restriction-modification system

A bacterial defence system in which restriction endonucleases cleave and inactivate specific target sequences in foreign DNA (for example, from phages); cleavage sites in host DNA are protected by methylation.

Leloir pathway

The predominant route of cellular galactose metabolism.

Opsonophagocytosis

A process by which a microorganism is labelled (opsonized) by host immune factors to facilitate uptake by phagocytic cells.

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Weiser, J.N., Ferreira, D.M. & Paton, J.C. Streptococcus pneumoniae: transmission, colonization and invasion. Nat Rev Microbiol 16, 355–367 (2018). https://doi.org/10.1038/s41579-018-0001-8

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