title: A coagulase-negative and non-haemolytic strain of Staphylococcus aureus for investigating the roles of SrtA in a murine model of bloodstream infection.
abstract: Sortase A (SrtA) is a cysteine transpeptidase and virulence factor from Staphylococcus aureus (S. aureus) that catalyses the attachment and display of surface proteins on the cell wall, thereby mediating bacterial adhesion to host tissues, host-cell entry and evasion of the immune response. As a result, SrtA has become an important target in the development of therapies for S. aureus infections. In this study, we used the new reference strain S. aureus Newman D2C to investigate the role of SrtA in a murine model of bloodstream infection, when the impact of coagulase and haemolysin is excluded. The results suggested that deletion of SrtA reduced the bacterial burden on the heart, liver and kidneys by blunting the host proinflammatory cytokine response at an early point in infection. Kidneys, but not heart or liver, formed abscesses on the sixth day following non-lethal infection, and this effect was diminished by SrtA mutation. These findings indicate that SrtA is a determining virulence factor in lethality and formation of renal abscesses in mice followed by S. aureus bloodstream infection. We have thus established a convenient in vitro and mouse model for developing SrtA-targeted therapeutic strategies.
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education/Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Animal Science, Jilin University, Changchun 130062, China.
authors.forename: Chongwei
authors.initials: C
authors.lastname: Bi
authors.affiliation: College of Animal Science, Jilin University, Changchun 130062, China.
authors.forename: Tiedong
authors.initials: T
authors.lastname: Wang
authors.affiliation: The College of Animal Science and Technology, Jilin Agricultural University, Changchun 130033, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Science, Harbin 150000, China.
authors.forename: Fuguang
authors.initials: F
authors.lastname: Chen
authors.affiliation: College of Animal Science, Jilin University, Changchun 130062, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.affiliation: College of Animal Science, Jilin University, Changchun 130062, China.
authors.forename: Bingrun
authors.initials: B
authors.lastname: Liu
authors.affiliation: The College of Animal Science and Technology, Jilin Agricultural University, Changchun 130033, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Cai
authors.affiliation: College of Animal Science, Jilin University, Changchun 130062, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Zoonosis Research, Ministry of Education/Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.affiliation: College of Animal Science, Jilin University, Changchun 130062, China wangdc@jlu.edu.cn.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Wang
mesh_terms: D000038:Abscess / Q000382:microbiology / Q000473:pathology; D019881:Aminoacyltransferases / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D016470:Bacteremia / Q000382:microbiology* / Q000473:pathology; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000378:metabolism*; D003030:Coagulase / Q000172:deficiency*; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006321:Heart / Q000382:microbiology; D006460:Hemolysin Proteins / Q000172:deficiency*; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development*; D016019:Survival Analysis; D037521:Virulence Factors / Q000172:deficiency / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003030:Coagulase; D006460:Hemolysin Proteins; D037521:Virulence Factors; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases
keywords: Sortase A; Staphylococcus aureus; mouse model; renal abscess