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Articles by Anna Scasny
Heme-Mediated Selection of Encapsulated Streptococcus pneumoniae in the Lungs by Oxidative Stress
Abstract Streptococcus pneumoniae (the pneumococcus) causes cytotoxicity and encapsulates within the lung parenchyma, leading to pneumococcal pneumonia. However, the underlying mechanisms remain unclear and likely involve multiple bacterial and host factors. We investigated the selection process of encapsulated pneumococci, a critical factor in lung damage during pneumococcal pneumonia. Our study revealed that pneumococci initially lack capsules but re-encapsulate upon reaching the alveoli.
Pneumococcal H₂O₂ Reshapes Mitochondrial Function and Reprograms Host Cell Metabolism
Abstract Streptococcus pneumoniae (Spn) is a primary cause of pneumonia, induces acute lung parenchymal infection, damaging through a unique metabolic pathway that generates hydrogen peroxide (H₂O₂) as a byproduct. This study reveals that Spn-derived H₂O₂, primarily produced by pyruvate oxidase (SpxB), inhibits the tricarboxylic acid (TCA) cycle in lung epithelial cells by targeting aconitase, glutamate dehydrogenase, and α-ketoglutarate dehydrogenase.
Oxidation of hemoglobin in the lung parenchyma facilitates the differentiation of pneumococci into encapsulated bacteria
Abstract Pneumococcal pneumonia causes cytotoxicity in the lung parenchyma but the underlying mechanism involves multiple factors contributing to cell death. Here, we discovered that hydrogen peroxide produced by Streptococcus pneumoniae (Spn-H2O2) plays a pivotal role by oxidizing hemoglobin, leading to its polymerization and subsequent release of labile heme. At physiologically relevant levels, heme selected a population of encapsulated pneumococci.
Oxidation of hemoproteins by Streptococcus pneumoniae collapses the cell cytoskeleton and disrupts mitochondrial respiration leading to cytotoxicity of human lung cells
New Results doi: https://doi.org/10.1101/2023.06.07.544089 Abstract Streptococcus pneumoniae (Spn) causes pneumonia that kills millions through acute toxicity and invasion of the lung parenchyma. During aerobic respiration, Spn releases hydrogen peroxide (Spn-H2O2), as a by-product of enzymes SpxB and LctO, and causes cell death with signs of both apoptosis and pyroptosis by oxidizing unknown cell targets. Hemoproteins are molecules essential for life and prone to oxidation by H2O2.
Synergistic Protection against Secondary Pneumococcal Infection by Human Monoclonal Antibodies Targeting Distinct Epitopes
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