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The Biology of Pneumolysin

  • Tim J. Mitchell
  • Catherine E. Dalziel
Chapter
Part of the Subcellular Biochemistry book series (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.

Keywords

Streptococcuspneumoniae Pneumolysin Pathogenesis of pneumococcal infection Meningitis Human respiratory epithelium Cell death 

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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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
  2. 2.School of Immunity and Infection, College of Medical and Dental SciencesUniversity of BirminghamBirminghamUK
  3. 3.Institute of Infection, Immunity and InflammationUniversity of GlasgowGlasgowUK

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