Next Article in Journal
The Use of Feed Additives to Reduce the Effects of Aflatoxin and Deoxynivalenol on Pig Growth, Organ Health and Immune Status during Chronic Exposure
Next Article in Special Issue
Earthworm-Derived Pore-Forming Toxin Lysenin and Screening of Its Inhibitors
Previous Article in Journal
Fluoxetine Induced Suicidal Erythrocyte Death
Previous Article in Special Issue
Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue
Article Menu

Export Article

Open AccessReview
Toxins 2013, 5(7), 1244-1260;

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

Vascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA
Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, USA
Division of Pulmonary Medicine, Georgia Regents University, Augusta, GA 30912, USA
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center and University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Institute of Medical Microbiology, Justus-Liebig University Giessen, D-35392, Germany
Authors to whom correspondence should be addressed.
Received: 31 May 2013 / Revised: 25 June 2013 / Accepted: 27 June 2013 / Published: 15 July 2013
(This article belongs to the Special Issue Pore-Forming Toxins)
Full-Text   |   PDF [1135 KB, uploaded 15 July 2013]   |  


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. View Full-Text
Keywords: pneumolysin; permeability edema; TNF; Growth Hormone-Releasing Hormone pneumolysin; permeability edema; TNF; Growth Hormone-Releasing Hormone

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Lucas, R.; Czikora, I.; Sridhar, S.; Zemskov, E.; Gorshkov, B.; Siddaramappa, U.; Oseghale, A.; Lawson, J.; Verin, A.; Rick, F.G.; Block, N.L.; Pillich, H.; Romero, M.; Leustik, M.; Schally, A.V.; Chakraborty, T. Mini-Review: Novel Therapeutic Strategies to Blunt Actions of Pneumolysin in the Lungs. Toxins 2013, 5, 1244-1260.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top