Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo

Shuai Meng; Zengping Xu; Xueming Wang; Yang Liu; Bole Li; Jie Zhang; Xiaolong Zhang; Tianjun Liu

doi:10.3389/fmicb.2023.1196072

Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo

Front Microbiol. 2023 Jun 8:14:1196072. doi: 10.3389/fmicb.2023.1196072. eCollection 2023.

Authors

Shuai Meng^{1

2}, Zengping Xu^{2

3}, Xueming Wang², Yang Liu², Bole Li¹, Jie Zhang¹, Xiaolong Zhang¹, Tianjun Liu²

Affiliations

¹ Department 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, China.
² Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
³ Center for Drug Evaluation, National Medical Products Administration, Beijing, China.

Abstract

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.

Keywords: Proteus mirabilis; cationic porphyrins; multi-drug resistant; photodynamic antimicrobial chemotherapy; photosensitizer.