Abstract:
Pneumolysin (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.
