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Here, we examined whether fosfomycin (FOM) could improve the bactericidal effect of phagocytes and investigated the potential mechanisms. FOM enhanced the phagocytosis and extra- or intracellular killing of <jats:italic>S. aureus<\/jats:italic> by phagocytes. And FOM enhanced the extracellular killing of <jats:italic>S. aureus<\/jats:italic> in macrophage (M\u0424) and in neutrophils mediated by extracellular traps (ETs). ET production was related to NADPH oxidase-dependent reactive oxygen species (ROS). Additionally, FOM increased the intracellular killing of <jats:italic>S. aureus<\/jats:italic> in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced <jats:italic>S. aureus<\/jats:italic> producing hydroxyl radicals in order to kill the bacterial cells <jats:italic>in vitro<\/jats:italic>. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity <jats:italic>in vivo<\/jats:italic> and FOM strengthened ROS and ET production from peritoneal lavage fluid <jats:italic>ex vivo<\/jats:italic>. An IVIS imaging system assay further verified the observed <jats:italic>in vivo<\/jats:italic> bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host\u2019s immune defences and antibiotic interactions in microbial infections.<\/jats:p>","DOI":"10.1038\/srep19262","type":"journal-article","created":{"date-parts":[[2016,1,18]],"date-time":"2016-01-18T11:53:49Z","timestamp":1453118029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species"],"prefix":"10.1038","volume":"6","author":[{"given":"Fengge","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,18]]},"reference":[{"key":"BFsrep19262_CR1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1574-6968.2010.01918.x","volume":"305","author":"KM Thompson","year":"2010","unstructured":"Thompson, K. 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