Mini-Review: Novel Therapeutic Strategies to Blunt Actions of Pneumolysin in the Lungs

Toxins

Rudolf Lucas¹  Istvan Czikora¹  Supriya Sridhar¹  Evgeny Zemskov¹  Boris Gorshkov¹  Umapathy Siddaramappa¹  Aluya Oseghale¹  Jonathan Lawson⁵  Alexander Verin¹  Ferenc G. Rick²  Norman L. Block²  Helena Pillich³  Maritza Romero⁴  Martin Leustik³  Andrew V. Schally² 

[1] Vascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA; E-Mails:;Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center and University of Miami, Miller School of Medicine, Miami, FL 33136, USA; E-Mails:;Institute of Medical Microbiology, Justus-Liebig University Giessen, D-35392, Germany; E-Mails:;Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, USA; E-Mail:;Division of Pulmonary Medicine, Georgia Regents University, Augusta, GA 30912, USA; E-Mail:

关键词: pneumolysin;    permeability edema;    TNF;    Growth Hormone-Releasing Hormone;   

DOI  :  10.3390/toxins5071244

来源: mdpi

【 摘 要 】

Severe pneumonia is the main single cause of death worldwide in children under five years of age. The main etiological agent of pneumonia is the G⁺ bacterium Streptococcus pneumoniae, which accounts for up to 45% of all cases. Intriguingly, patients can still die days after commencing antibiotic treatment due to the development of permeability edema, although the pathogen was successfully cleared from their lungs. This condition is characterized by a dramatically impaired alveolar epithelial-capillary barrier function and a dysfunction of the sodium transporters required for edema reabsorption, including the apically expressed epithelial sodium channel (ENaC) and the basolaterally expressed sodium potassium pump (Na⁺-K⁺-ATPase). The main agent inducing this edema formation is the virulence factor pneumolysin, a cholesterol-binding pore-forming toxin, released in the alveolar compartment of the lungs when pneumococci are being lysed by antibiotic treatment or upon autolysis. Sub-lytic concentrations of pneumolysin can cause endothelial barrier dysfunction and can impair ENaC-mediated sodium uptake in type II alveolar epithelial cells. These events significantly contribute to the formation of permeability edema, for which currently no standard therapy is available. This review focuses on discussing some recent developments in the search for the novel therapeutic agents able to improve lung function despite the presence of pore-forming toxins. Such treatments could reduce the potentially lethal complications occurring after antibiotic treatment of patients with severe pneumonia.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.