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Int. J. Mol. Sci. 2018, 19(4), 1147; https://doi.org/10.3390/ijms19041147

Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia

1
Department of Immunology and Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa
2
Department of Haematology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria 0001, South Africa
3
Division of Pulmonology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 0002, South Africa
*
Author to whom correspondence should be addressed.
Received: 22 February 2018 / Revised: 14 March 2018 / Accepted: 21 March 2018 / Published: 11 April 2018
(This article belongs to the Special Issue Bacterial Protein Toxins: Enemies within or Unexpected Friends)
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Abstract

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY. View Full-Text
Keywords: cardiovascular events; cholesterol-dependent cytolysins; community-acquired pneumonia; liposomes; macrolide antibiotics; neutrophils; neutrophil extracellular traps; platelets; pneumolysin antagonists; vaccines cardiovascular events; cholesterol-dependent cytolysins; community-acquired pneumonia; liposomes; macrolide antibiotics; neutrophils; neutrophil extracellular traps; platelets; pneumolysin antagonists; vaccines
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Anderson, R.; Nel, J.G.; Feldman, C. Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia. Int. J. Mol. Sci. 2018, 19, 1147.

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