Abstract
Pseudomonas aeruginosa is an important opportunistic pathogen responsible for the cause of acute lung injury and acute respiratory distress syndrome. P. aeruginosa isthe leading species isolated from patients with nosocomial infection and is detected in almost all the patients with long term ventilation in critical care units. P. aeruginosa infection is also the leading cause of deleterious chronic lung infections in patients suffering from cystic fibrosis as well as the major reason for morbidity in people with chronic obstructive pulmonary disease. P. aeruginosa infections are linked to diseases with high mortality rates and are challenging for treatment, for which no effective remedies have been developed. Massive lung epithelial cell death is a hallmark of severe acute lung injury and acute respiratory distress syndrome caused by P. aeruginosa infection. Lung epithelial cell death poses serious challenges to air barrier and structural integrity that may lead to edema, cytokine secretion, inflammatory infiltration, and hypoxia. Here we review different types of cell death caused by P. aeruginosa serving as a starting point for the diseases it is responsible for causing. We also review the different mechanisms of cell death and potential therapeutics in countering the serious challenges presented by this deadly bacterium.
Highlights
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are a severe public concern worldwide
The importance of each pathway should be weighted in the pathogenesis of cell death by P. aeruginosa
Several attempts have been thrown into targeting P. aeruginosa induced cell death, these include IL–15, platelet factors, chromatin modulator Mortality factor 4 like 1 (Morf4l1), or LPS antagonists
Summary
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are a severe public concern worldwide. P. aeruginosa is present in the respiratory tract of many of the patients with long-term ventilation more than 7 days [2] It is the leading cause of deleterious chronic lung infections in patients suffering from cystic fibrosis (CF) [3]. The replication and colonization of the invaded bacteria may physically damage the integrity of the lung epithelial cells. The bacteria cause host inflammatory response via multiple channels of molecular mechanisms that induce lung epithelial cell death. P. aeruginosa infection mediated lung epithelial cell death destroys the integrity of the air–blood barrier, and leads to leaks and edema, that will attract peripheral circulating neutrophils, microphages, and lymphocyte infiltration and enhance inflammatory response. Our understanding on the underlying molecular mechanisms of P. aeruginosa induced lung epithelial cell death is yet to be studied for the development of an effective therapy against the pathogen and the related illnesses
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