Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo
For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of am...
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Frontiers Media S.A.
2023-06-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1196072/full |
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author | Shuai Meng Shuai Meng Zengping Xu Zengping Xu Xueming Wang Yang Liu Bole Li Jie Zhang Xiaolong Zhang Tianjun Liu |
author_facet | Shuai Meng Shuai Meng Zengping Xu Zengping Xu Xueming Wang Yang Liu Bole Li Jie Zhang Xiaolong Zhang Tianjun Liu |
author_sort | Shuai Meng |
collection | DOAJ |
description | For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection. |
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issn | 1664-302X |
language | English |
last_indexed | 2024-03-12T16:46:06Z |
publishDate | 2023-06-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Microbiology |
spelling | doaj.art-f808080a35044e649721bd2be30870562023-08-08T13:53:03ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-06-011410.3389/fmicb.2023.11960721196072Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivoShuai Meng0Shuai Meng1Zengping Xu2Zengping Xu3Xueming Wang4Yang Liu5Bole Li6Jie Zhang7Xiaolong Zhang8Tianjun Liu9Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaTianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaTianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaCenter for Drug Evaluation, National Medical Products Administration, Beijing, ChinaTianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaTianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaDepartment of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, ChinaTianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaFor the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1196072/fullphotodynamic antimicrobial chemotherapyphotosensitizercationic porphyrinsProteus mirabilismulti-drug resistant |
spellingShingle | Shuai Meng Shuai Meng Zengping Xu Zengping Xu Xueming Wang Yang Liu Bole Li Jie Zhang Xiaolong Zhang Tianjun Liu Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo Frontiers in Microbiology photodynamic antimicrobial chemotherapy photosensitizer cationic porphyrins Proteus mirabilis multi-drug resistant |
title | Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo |
title_full | Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo |
title_fullStr | Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo |
title_full_unstemmed | Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo |
title_short | Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo |
title_sort | synthesis and photodynamic antimicrobial chemotherapy against multi drug resistant proteus mirabilis of ornithine porphyrin conjugates in vitro and in vivo |
topic | photodynamic antimicrobial chemotherapy photosensitizer cationic porphyrins Proteus mirabilis multi-drug resistant |
url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1196072/full |
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