Anderson, RonaldNel, Jan GertFeldman, Charles2018-06-012018-06-012018-04-11Anderson, R., Nel, J.G. & Feldman, C. 2018, 'Multifaceted role of pneumolysin in the pathogenesis of myocardial injury in community-acquired pneumonia', International Journal of Molecular Sciences, vol. 19, no. 4, art. no. 1147, pp. 1-22.1422-0067 (online)10.3390/ijms19041147http://hdl.handle.net/2263/65071Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, -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.en© 2018 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).Cardiovascular eventsCholesterol-dependent cytolysinsLiposomesMacrolide antibioticsNeutrophilsNeutrophil extracellular trapsPlateletsPneumolysin antagonistsVaccinesPneumolysin (PLY)Community-acquired pneumonia (CAP)Article