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

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.

SUBMITTER: Anderson R

PROVIDER: S-EPMC5979279 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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

Anderson Ronald R Nel Jan G JG Feldman Charles C

International journal of molecular sciences 20180411 4

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, <i>Streptococcus pneumoniae</i> (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. Notwithstand ...[more]

PMID: 29641429

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Project description:Background: Severe community-acquired pneumonia (sCAP) is the most frequent admission for acute respiratory failure in intensive care medicine. Observational studies have found a correlation between patients who were admitted with CAP and the development of cardiovascular events. The risk of acute myocardial damage in patients with CAP is particularly high within the first 30 days of hospitalization. Research design and methods: Multicenter prospective cohort analysis conducted in consecutive patients admitted to an ICU with microbiologically confirmed diagnoses of sCAP. The aim was to determine any structural cardiac damage detected by advanced imagining techniques (cardiac MRI) and cardiac biomarkers in patients with sCAP. The patients were stratified, according to their etiology, into pneumococcal or not-pneumococcal sCAP. The primary outcome was cardiac damage at day 5 and 7 of clinical presentation. Results: A total of 23 patients were consecutively and prospectively enrolled for two winter periods. No significant differences were observed between the median troponin when comparing the pneumococcal vs. non-pneumococcal. The incidence of myocardial damage was numerically higher in the pneumococcal subgroup (70% vs. 50%, p = 0.61) on day 5 and on day 7 (53% vs. 40%, p = 0.81) but did not achieve significance. Confirming a correlation between the biomarkers of cell damage and the biomarkers of myocardial damage, only a positive and significant correlation was observed between h-FABP and DNA on day 1 (r = 0.74; p < 0.01) and day 3 (r = 0.83; p < 0.010). Twenty cardiac MRIs were performed on the 23 patients (87%). No presence of fibrosis was observed in any of the studies carried out within the first 15 days of admission. Conclusions: No significant myocardial damage was found in patients with sCAP independent of the bacterial etiology in accordance with biomarker alterations (Troponin and/or h-FABP) or cardiac MRI. Using cardiac MRI, we could not find any presence of myocardial fibrosis within the first 15 days of admission.

Dataset Information

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

Publications

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

Similar Datasets

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