title: Recombinant lysostaphin protects mice from methicillin-resistant Staphylococcus aureus pneumonia.
abstract: The advent of methicillin-resistant Staphylococcus aureus (MRSA) and the frequent and excessive abuse of ventilators have made MRSA pneumonia an inordinate threat to human health. Appropriate antibacterial therapies are crucial, including the use of lysostaphin as an alternative to antibiotics. To explore the potential use of lysostaphin as a therapeutic agent for MRSA pneumonia, mice were intranasally infected with MRSA and then treated with recombinant lysostaphin (rLys; 45 mg/kg in the high-dose group and 1 mg/kg in the low-dose group) (0.33 mg/mL, 15 mg/mL), vancomycin (120 mg/kg) (40 mg/mL), or phosphate-buffered saline (PBS, negative control) 4 h after infection. Therapeutic efficacy was assessed by mouse survival, lung histopathology, bacterial density in the lungs, bodyweight, lung weight, temperature, white blood cells counts, lymphocytes counts, granulocytes counts, and monocytes counts. The mice treated with rLys showed lower mortality, less lung parenchymal damage, and lower bacterial density at metastatic tissue sites than mice treated with PBS or vancomycin. The overall mortality was 100%, 60%, 40%, and 60% for the control, vancomycin, high-dose rLys, and low-dose rLys groups, respectively. These findings indicate that, as a therapeutic agent for MRSA pneumonia, lysostaphin exerts profound protective effects in mice against the morbidity and mortality associated with S. aureus pneumonia.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China ; Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China ; Anhui Medical University, Hefei 230032, China ; Laboratory of Gene Regulation, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Chen
authors.identifier: 0000-0002-3943-184X
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China ; Department of Microbiology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Huahao
authors.identifier: 0000-0001-5007-2158
authors.initials: H
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.
authors.forename: Fan
authors.identifier: 0000-0001-9264-8469
authors.initials: F
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.
authors.forename: Hang
authors.identifier: 0000-0002-7927-1684
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.
authors.forename: Yigang
authors.identifier: 0000-0002-8503-8045
authors.initials: Y
authors.lastname: Tong
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001772:Blood Cell Count; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008248:Lysostaphin / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus; D051379:Mice; D008807:Mice, Inbred BALB C; D011023:Pneumonia, Staphylococcal / Q000097:blood / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D014640:Vancomycin; D008248:Lysostaphin