title: Enzyme activated photodynamic therapy for methicillin-resistant Staphylococcus aureus infection both inv itro and in vivo.
abstract: In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most common multi-drug resistant bacteria in both hospital and community. The aim of this study is to investigate the selective inhibition of MRSA by a modified photosensitizer (LAEtNBS) in vitro and the efficacy of MRSA infection treatment by photodynamic therapy (PDT) with LAEtNBS in vivo. LAEtNBS was synthesized by adding a cationic photosensitizer molecule (EtNBS-COOH) and a quencher molecule to two side chains of cephalosporin, which was then shown to have similar absorption and emission wavelengths with EtNBS-COOH, but suppressed yields of fluorescence quantum and singlet oxygen. The selective inactivation and less phototoxicity of LAEtNBS, compared to that of EtNBS-COOH, were assessed and confirmed by conducting PDT to two Staphylococcus aureus strains and human skin cells at a fluence of 15 J/cm(2) with 640±10 nm LED light. Furthermore, using mouse skin wound model infected with 10(8) CFU of MRSA, we found that both LAEtNBS and EtNBS-COOH were able to treat MRSA infection and enhance wound repair. However, there was no significant difference in the two photosensitizers that might be due to the environment in vivo. Modification of the photosensitizer will be very beneficial for developing new strategies to treat drug resistant bacterial infection with less harm to host tissue.
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Fu
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 201804, China.
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Zhu
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
authors.forename: Yin-Bo
authors.initials: YB
authors.lastname: Peng
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
authors.forename: You-Shuang
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hu
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
authors.forename: Hua-Xiang
authors.initials: HX
authors.lastname: Lu
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
authors.forename: Wei-Rong
authors.initials: WR
authors.lastname: Yu
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 201804, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Du
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, and Institute of Traumatic Medicine; School of Medicine, Shanghai Jiao Tong University, Shanghai 201900, China; Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: my058@vip.sina.com.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002478:Cells, Cultured; D002511:Cephalosporins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005347:Fibroblasts; D006801:Humans; D008027:Light; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000293:injuries; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects; D001618:beta-Lactamases
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D017319:Photosensitizing Agents; D001618:beta-Lactamases
keywords: Methicillin-resistant Staphylococcus aureus; Photodynamic therapy; Skin wound infection; Wound healing