XXXX secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells.

@entity1 @entity5568 @entity697 @entity137 @entity55 @entity2260 @entity15664 @entity1129 @entity204 @entity328 @entity2388
UNASSIGNED: @entity328 is a leading cause of @entity55 and one of the most common causes of @entity204 globally. The impact of @entity2260 on host molecular processes that lead to detrimental pulmonary consequences is not fully understood. Here, we show that @entity2260 induces toxic DNA double-strand breaks (DSBs) in @entity1 alveolar epithelial cells, as indicated by @entity1129 mutated kinase (ATM)-dependent phosphorylation of histone H2AX and colocalization with p53-binding protein ( @entity15664 ). Furthermore, results show that DNA damage occurs in a bacterial contact-independent fashion and that @entity328 @entity2388 oxidase (SpxB), which enables synthesis of @entity5568 , plays a critical role in inducing DSBs. The extent of DNA damage correlates with the extent of apoptosis, and DNA damage precedes apoptosis, which is consistent with the time required for execution of apoptosis. Furthermore, addition of catalase, which neutralizes @entity5568 , greatly suppresses @entity2260 -induced DNA damage and apoptosis. Importantly, @entity2260 induces DSBs in the lungs of animals with @entity697 , and @entity5568 production by @entity2260 in vivo contributes to its genotoxicity and virulence. One of the major DSBs repair pathways is nonhomologous end joining for which Ku70/80 is essential for repair. We find that deficiency of Ku80 causes an increase in the levels of DSBs and apoptosis, underscoring the importance of DNA repair in preventing @entity2260 -induced genotoxicity. Taken together, this study shows that @entity2260 -induced damage to the host cell genome exacerbates its @entity137 and pathogenesis, making DNA repair a potentially important susceptibility factor in @entity1 who suffer from @entity55 .
