Dual Role of Hydrogen Peroxide As an Oxidant in Pneumococcal Pneumonia

(), a facultative anaerobic Gram-positive human pathogen with increasing rates of penicillin and macrolide resistance, is a major cause of lower respiratory tract infections worldwide. Pneumococci are a primary agent of severe pneumonia in children younger than 5 years and of community-acquired pneumonia in adults. A major defense mechanism toward is the generation of reactive oxygen species, including hydrogen peroxide (HO), during the oxidative burst of neutrophils and macrophages. Paradoxically, produces high endogenous levels of HO as a strategy to promote colonization. Pneumococci, which express neither catalase nor common regulators of peroxide stress resistance, have developed unique mechanisms to protect themselves from HO. generates high levels of HO as a strategy to promote colonization. Production of HO moreover constitutes an important virulence phenotype and its cellular activities overlap and complement those of other virulence factors, such as pneumolysin, in modulating host immune responses and promoting organ injury. This review examines the dual role of HO in pneumococcal pneumonia, from the viewpoint of both the pathogen (defense mechanisms, lytic activity toward competing pathogens, and virulence) and the resulting host-response (inflammasome activation, endoplasmic reticulum stress, and damage to the alveolar-capillary barrier in the lungs). An understanding of the complexity of HO-mediated host-pathogen interactions is necessary to develop novel strategies that target these processes to enhance lung function during severe pneumonia.