Protective Role ofd-Amino Acid Oxidase against Staphylococcus aureus Infection

Abstract

<jats:title>ABSTRACT</jats:title><jats:p><jats:sc>d</jats:sc>-Amino acid oxidase (DAO) is a hydrogen peroxide-generating enzyme that uses a<jats:sc>d</jats:sc>-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<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Staphylococcus aureus</jats:named-content>in a manner that depended on the concentration of DAO and<jats:sc>d</jats:sc>-amino acid<jats:italic>in vitro</jats:italic>. Addition of catalase abolished the bacteriostatic activity of DAO. Although DAO plus<jats:sc>d</jats:sc>-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<jats:sc>d</jats:sc>-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.<jats:italic>In vivo</jats:italic>experiments showed that DAO<jats:sup>−/−</jats:sup>(mutant) mice were more susceptible to<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. aureus</jats:named-content>infection than were DAO<jats:sup>+/+</jats:sup>(wild-type) mice. These results suggest that DAO, together with myeloperoxidase, may play an important role in antibacterial systems in mammals.</jats:p>

Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology

“…168,169 A later study showed that DAO is localized in the neutrophilic surface, internalized during phagocytosis, and is capable of H 2 O 2 production within the phagosome. 170 Mice lacking DAO activity were shown to be more susceptible to intravenous injection with Staphylococcus aureus, 171 supporting a role for neutrophilic DAO in systemic innate defense that is responsive to microbial input. More recently, microbial d-amino acids also have been associated with the immune system in the mucosa.…”

Interplay between microbial d-amino acids and host d-amino acid oxidase modifies murine mucosal defence and gut microbiota

“…Previous studies have suggested that DAO may contribute to systemic defense against pathogens via the activity of neutrophil DAO 18,19 . To test whether DAO activity is important to mucosal defense in vivo, we explored the effect of DAO and D-aa on V. cholerae intestinal colonization in streptomycin-treated adult mice.…”

D-Amino Acids and Their Oxidase in Farm Animals — The Role and Opportunities

“…This paradoxical observation needs clarification, since both enzymes are capable of decomposing H 2 O 2 , but the physiological effect of their combined action is antipodal. Nevertheless, it is reliably known that an increase in the D-serine level and a decrease in DAAO activity are efficient in treating various diseases, including mental disorders and oncological ones [40][41][42][43][44][45].…”