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The pathogenesis of streptococcal infections: from Tooth decay to meningitis

Nature Reviews Microbiology volume 1, pages 219–230 (2003)Cite this article

Key Points

  • Streptococci are often carried on mucosal surfaces and skin without causing disease.

  • Streptococci can cause diseases that range from dental caries to necrotizing fasciitis. The type of disease caused depends on the virulence factors produced by the bacterium, as well as host susceptibility.

  • Streptococcus mutans causes dental caries; this requires the ability of this organism to form biofilms and to produce acid on the tooth surface.

  • Streptococcus agalactiae — group B streptococcus (GBS) — can cause neonatal meningitis. The organism is usually acquired by the neonate during passage through the birth canal of a colonized mother. Key virulence factors are the capsule, surface proteins and a haemolysin.

  • Streptococcus pyogenes — group A streptococcus (GAS) — can cause a wide range of diseases. Toxic-shock syndrome that is caused by this organism is mediated by the production of superantigens. The organism makes a capsule, a wide range of toxins and enzymes, and molecules that interfere with innate immunity.

  • Streptococcus pneumoniae (the pneumococcus) can cause pneumonia and meningitis. The organism induces overactivation of the inflammatory response, and disease symptoms partly reflect inappropriate production of host immune mediators. Key virulence factors are the capsule, surface proteins and pneumolysin.

  • Complete genome sequences are available for nine strains of these four species of streptococci (one for S. mutans, two for GBS, four for GAS and two for pneumococcus). Analysis of the genes present in all four species shows that the highly conserved genes are concerned with core function, such as nucleic-acid metabolism and protein synthesis. There is also significant variation in gene content, even between strains of the same species.

  • Simultaneous analysis of expression of all genes in the genome is now possible using microarray technology. It is also possible to examine the expression of genes in organisms that cause infection in model systems or in human disease. Such studies are beginning to allow an understanding of the detailed interactions that occur between pathogens and their hosts.

Abstract

The development of bacterial disease has been likened to a 'molecular arms race', in which the host tries to eliminate the bacteria, while the bacteria try to survive in the host. Although most bacteria do not cause disease, some cause serious human infection in a large proportion of encounters. Between these two extremes are bacteria that can coexist with humans in a carriage state but, under appropriate circumstances, cause disease. The streptococci exemplify this group of organisms, and by studying them we can begin to address why bacteria cause such a wide spectrum of disease.

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Figure 1: Summary of the main virulence factors of four streptococcal species.
Figure 2: The complement system.
Figure 3: Genomic comparisons between streptococcal species.

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Authors and Affiliations

  1. Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK

    Timothy J. Mitchell

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DATABASES

Entrez

CylE

EndoS

FBP54

FbsA

GRAB

Lmb

M-protein

pneumolysin

PsaA

PspA

PspC

SLO

SloC

SpaP

SpeB

FURTHER INFORMATION

Comprehensive Microbial Resource

Infectious disease information

GAS

GBS

Streptococcus pneumoniae

Tim Mitchell's web site

Glossary

ENDOCARDITIS

Inflammation of the lining of the heart and its valves.

TWO-COMPONENT SIGNAL-TRANSDUCTION PATHWAY

A signal-transduction system that consists of a sensor protein that senses and responds to an external signal, and which acts on a response-regulator protein that transmits the signal to other components of the cell.

LECTIN

A cell-agglutinating protein of non-immune origin, which binds carbohydrates without modifying them.

PASSIVE IMMUNIZATION

The induction of immunity by the transfer of immunoglobulins or T cells.

SORTASE

An enzyme that links proteins to the cell wall.

HYDROXYAPATITE

The main mineral component of teeth.

GLUCOSYLTRANSFERASE

Any hexosyltransferase enzyme for which the glycosyl group transferred is glucosyl.

GERM-FREE RATS

Rats bred and maintained in such conditions that they contain no microorganisms.

SIGNATURE-TAGGED MUTAGENESIS

A negative selection method for the identification of virulence genes. The technique involves mutation of microbial genes by random insertion of a tagged transposon. After growth of a mixed population in a host, mutated genes that are absent and hence required for virulence are identified with the help of the tag.

OPSONOPHAGOCYTOSIS

Increased uptake of bacteria by host cells due to binding of antibody or complement.

β-HAEMOLYSIS

Zone of clearing around bacterial colonies grown on blood agar, caused by lysis of red blood cells.

HAEMOLYSIN

Material that lyses red blood cells.

ENDOGLYCOSIDASE

An enzyme that hydrolyses non-terminal glycosidic linkages in oligosaccharides or polysaccharides.

MEMBRANE-ATTACK COMPLEX

A collection of late complement components that damage the cell membrane.

PYOGENIC EXOTOXINS

Toxins that induce fever.

SUPERANTIGEN

A protein that activates T cells non-specifically.

STREPTOCOCCAL TOXIC-SHOCK SYNDROME

A disease associated with decreased blood pressure and multi-organ failure.

EPENDYMAL CILIA

Specialized ciliated cells that line the ventricles of the brain.

ENOLASE

Also known as phosphopyruvate hydratase. An enzyme that catalyses the conversion of 2-phospho-D-glycerate to phosphoenolpyruvate and water.

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Mitchell, T. The pathogenesis of streptococcal infections: from Tooth decay to meningitis. Nat Rev Microbiol 1, 219–230 (2003). https://doi.org/10.1038/nrmicro771

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