Pneumolysin as a potential therapeutic target in severe pneumococcal disease

dc.contributor.authorAnderson, Ronald
dc.contributor.authorFeldman, Charles
dc.contributor.emailronald.anderson@up.ac.zaen_ZA
dc.date.accessioned2017-07-31T08:57:25Z
dc.date.issued2017-06
dc.description.abstractAcute pulmonary and cardiac injury remain significant causes of morbidity and mortality in those afflicted with severe pneumococcal disease, with the risk for early mortality often persisting several years beyond clinical recovery. Although remaining to be firmly established in the clinical setting, a considerable body of evidence, mostly derived from murine models of experimental infection, has implicated the pneumococcal, cholesterol-binding, pore-forming toxin, pneumolysin (Ply), in the pathogenesis of lung and myocardial dysfunction. Topics covered in this review include the burden of pneumococcal disease, risk factors, virulence determinants of the pneumococcus, complications of severe disease, antibiotic and adjuvant therapies, as well as the structure of Ply and the role of the toxin in disease pathogenesis. Given the increasing recognition of the clinical potential of Ply-neutralisation strategies, the remaining sections of the review are focused on updates of the types, benefits and limitations of currently available therapies which may attenuate, directly and/or indirectly, the injurious actions of Ply. These include recently described experimental therapies such as various phytochemicals and lipids, and a second group of more conventional agents the members of which remain the subject of ongoing clinical evaluation. This latter group, which is covered more extensively, encompasses macrolides, statins, corticosteroids, and platelet-targeted therapies, particularly aspirin.en_ZA
dc.description.departmentImmunologyen_ZA
dc.description.embargo2018-06-30
dc.description.librarianhj2017en_ZA
dc.description.sponsorshipThe National Research Foundation of South Africaen_ZA
dc.description.urihttp://www.elsevierhealth.com/journals/jinfen_ZA
dc.identifier.citationAnderson, R. & Feldman, C. 2017, 'Pneumolysin as a potential therapeutic target in severe pneumococcal disease', Journal of Infection, vol. 74, no. 6, pp. 527-544.en_ZA
dc.identifier.issn1532-2742 (online)
dc.identifier.issn0163-4453 (print)
dc.identifier.other10.1016/j.jinf.2017.03.005
dc.identifier.urihttp://hdl.handle.net/2263/61525
dc.language.isoenen_ZA
dc.publisherElsevieren_ZA
dc.rights© 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Journal of Infection. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in Journal of Infection, vol. 74, no. 6, pp. 527-544, 2017. doi : 10.1016/j.jinf.2017.03.005.en_ZA
dc.subjectAspirinen_ZA
dc.subjectCorticosteroidsen_ZA
dc.subjectMacrolidesen_ZA
dc.subjectPneumococcusen_ZA
dc.subjectStatinsen_ZA
dc.subjectStreptococcus pneumoniaeen_ZA
dc.subjectVorapaxaren_ZA
dc.subjectProtease-activated receptor 1en_ZA
dc.titlePneumolysin as a potential therapeutic target in severe pneumococcal diseaseen_ZA
dc.typePostprint Articleen_ZA

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