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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Main Authors: Shuai Meng, Zengping Xu, Xueming Wang, Yang Liu, Bole Li, Jie Zhang, Xiaolong Zhang, Tianjun Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Microbiology
Subjects:
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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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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