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The Biology of Pneumolysin

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MACPF/CDC Proteins - Agents of Defence, Attack and Invasion

Part of the book series: Subcellular Biochemistry ((SCBI,volume 80))

Abstract

Cholesterol dependent cytolysins are important in the ability of some bacteria to cause disease in man and animals. Pneumolysin (PLY) plays a key role in the diseases caused by Streptococcus pneumoniae (the pneumococcus). This chapter describes the role of PLY in some of the key process in disease. These include induction of cell death by pore formation and toxin-induced apoptosis as well as more subtle effects on gene expression of host cells including epigenetic effects of the toxin. The use of bacterial mutants that either do not express the toxin or express altered versions in biological systems is described. Use of isolated tissue and whole animal systems to dissect the structure/function relationships of the toxin as well as the role played by different activities in the pathogenesis of infection are described. The role of PLY in meningitis and the associated deafness is discussed as well as the role of the toxin in promoting increased lung permeability and inflammation during pneumococcal pneumonia. Different clinical strains of the pneumococcus produce different forms of PLY and the impact of this on disease caused by these strains is discussed. Finally, the impact of this knowledge on the development of treatment and prevention strategies for pneumococcal disease is discussed.

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Abbreviations

AIF:

Apoptosis-inducing factor

CDC:

Cholesterol dependent cytolysin

CFU:

Colony forming units

CRP:

C-reactive protein

CYLD:

Deubiquitinating enzyme cylindromatosis

D1–3:

Domains 1–3

HBMEC:

Human brain microvascular endothelial cells

ICAM-1:

Intracellular adhesion molecule-1

MAC:

Membrane attack complex

NALP3:

NOD-like receptor family pyrin domain containing 3

p38-MAPK:

p38 mitogen-activated protein kinase

PAI-1:

Plasminogen activator-1

PI3K:

Phosphoinositide-3-kinase

PKC:

Protein kinase-C

PLY:

Pneumolysin

ROCK:

Rho-associated kinase

SDM:

Site-directed mutagenesis

TLO:

Tetanolysin

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Authors and Affiliations

  1. Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15-2TT, UK

    Tim J. Mitchell

  2. School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B5-2TT, UK

    Tim J. Mitchell

  3. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12-8TA, UK

    Catherine E. Dalziel

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Correspondence to Tim J. Mitchell .

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  1. National Institute of Chemistry, Ljubljana, Slovenia, Laboratory for Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia

    Gregor Anderluh

  2. Division of Structural Biology, University of Oxford Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom

    Robert Gilbert

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Mitchell, T.J., Dalziel, C.E. (2014). The Biology of Pneumolysin. In: Anderluh, G., Gilbert, R. (eds) MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Subcellular Biochemistry, vol 80. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8881-6_8

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