title: Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species.
abstract: The successful treatment of bacterial infections is the achievement of a synergy between the host's immune defences and antibiotics. 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 S. aureus by phagocytes. And FOM enhanced the extracellular killing of S. aureus in macrophage (MФ) 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 S. aureus in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced S. aureus producing hydroxyl radicals in order to kill the bacterial cells in vitro. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity in vivo, and FOM strengthened ROS and ET production from peritoneal lavage fluid ex vivo. An IVIS imaging system assay further verified the observed in vivo bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host's immune defences and antibiotic interactions in microbial infections.
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Fengge
authors.initials: F
authors.lastname: Shen
authors.affiliation: Key Lab for New Drug Research of TCM, Research Institute of Tsinghua University in Shenzhen, Shenzhen, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Changchun, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Shi
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: An
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.|Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, The First Hospital of Jilin University, College of Veterinary Medicine and College of Animal Science, Jilin University, Changchun, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D065206:Extracellular Traps / Q000187:drug effects / Q000276:immunology; D005578:Fosfomycin / Q000008:administration & dosage*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology
chemical_list: D017382:Reactive Oxygen Species; D005578:Fosfomycin