Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Science, Sojo University, Ikeda, Kumamoto, Japan.
Infect Immun. 2012 Apr;80(4):1546-53. doi: 10.1128/IAI.06214-11. Epub 2012 Jan 23.
D-Amino acid oxidase (DAO) is a hydrogen peroxide-generating enzyme that uses a D-amino acid as a substrate. We hypothesized that DAO may protect against bacterial infection, because hydrogen peroxide is one of the most important molecules in the antibacterial defense systems in mammals. We show here that DAO suppressed the growth of Staphylococcus aureus in a manner that depended on the concentration of DAO and D-amino acid in vitro. Addition of catalase abolished the bacteriostatic activity of DAO. Although DAO plus D-Ala showed less bactericidal activity, addition of myeloperoxidase (MPO) greatly enhanced the bactericidal activity of DAO. Furthermore, DAO was able to utilize bacterial lysate, which contains D-Ala derived from peptidoglycan; this could produce hydrogen peroxide with, in the presence of myeloperoxidase, formation of hypochlorous acid. This concerted reaction of DAO and MPO led to the bactericidal action. In vivo experiments showed that DAO(-/-) (mutant) mice were more susceptible to S. aureus infection than were DAO(+/+) (wild-type) mice. These results suggest that DAO, together with myeloperoxidase, may play an important role in antibacterial systems in mammals.
D-氨基酸氧化酶（DAO）是一种产生过氧化氢的酶，它以 D-氨基酸为底物。我们假设 DAO 可能具有抵抗细菌感染的作用，因为过氧化氢是哺乳动物抗菌防御系统中最重要的分子之一。我们在这里表明，DAO 可以在体外依赖 DAO 和 D-氨基酸的浓度抑制金黄色葡萄球菌的生长。添加过氧化氢酶可消除 DAO 的抑菌活性。虽然 DAO 加 D-Ala 的杀菌活性较低，但添加髓过氧化物酶（MPO）可大大增强 DAO 的杀菌活性。此外，DAO 能够利用细菌裂解物，其中包含来自肽聚糖的 D-Ala；在髓过氧化物酶存在下，这可以产生次氯酸。DAO 和 MPO 的协同反应导致了杀菌作用。体内实验表明，DAO(-/-)（突变）小鼠比 DAO(+/+)（野生型）小鼠更容易感染金黄色葡萄球菌。这些结果表明，DAO 与髓过氧化物酶一起可能在哺乳动物的抗菌系统中发挥重要作用。
