Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis
IntroductionIn previous research, antibacterial photodynamic therapy using lysine-porphyrin conjugate LD4 effectively inactivated methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli; however, it exhibited limited activity against Candida albicans and Mycobacteri...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1626193/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849253663098273792 |
|---|---|
| author | Xueming Wang Zhonghua Qin Ying Wen Mingxuan Chi Lixia Zhang Junping Wu Tianjun Liu |
| author_facet | Xueming Wang Zhonghua Qin Ying Wen Mingxuan Chi Lixia Zhang Junping Wu Tianjun Liu |
| author_sort | Xueming Wang |
| collection | DOAJ |
| description | IntroductionIn previous research, antibacterial photodynamic therapy using lysine-porphyrin conjugate LD4 effectively inactivated methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli; however, it exhibited limited activity against Candida albicans and Mycobacterium tuberculosis.MethodsTo address this limitation, we developed a synergistic antibacterial strategy by combining LD4 with Cu2+ or Zn2+.ResultsSynergy was confirmed via minimum inhibitory concentration and fractional inhibitory concentration index analyses, demonstrating 16- to 64-fold enhanced antibacterial efficacy compared to LD4 alone. Mechanistic studies revealed divergent pathways for LD4 + Cu2+ and LD4 + Zn2+: Zn2+ increased the reactive oxygen species yield and promoted LD4 uptake by pathogens, while LD4 + Cu2+ induced oxidative damage to cell walls and membranes in darkness, with light exposure exacerbating structural damage. Cytotoxicity assessments confirmed low toxicity, with >90% survival of normal cells at bactericidal concentrations. Fluorescence and infrared spectroscopy characterized metal-LD4 complexes, showing stabilization through interactions between amino and pyrrolic imino groups of LD4 and metal ions, which promoted non-radiative transitions and fluorescence quenching. Both combinations caused significant bacterial membrane disruption and growth suppression. Notably, cytotoxicity exhibited a biphasic dose-response linked to metal-LD4 complexation-dependent particle size changes.DiscussionThis study elucidated the enhanced antimicrobial mechanisms and safety of LD4-metal ion combinations. The findings resolve the limitations of LD4 while providing a theoretical framework for developing novel therapies against fungal and mycobacterial infections. |
| format | Article |
| id | doaj-art-ca4863a4fc984ee6a1e2b57e67c791f1 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-ca4863a4fc984ee6a1e2b57e67c791f12025-08-20T03:56:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16261931626193Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosisXueming Wang0Zhonghua Qin1Ying Wen2Mingxuan Chi3Lixia Zhang4Junping Wu5Tianjun Liu6State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, ChinaTuberculosis Precision Testing Center, Tianjin Haihe Hospital, Tianjin, ChinaState Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, ChinaTuberculosis Precision Testing Center, Tianjin Haihe Hospital, Tianjin, ChinaTuberculosis Precision Testing Center, Tianjin Haihe Hospital, Tianjin, ChinaState Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, ChinaIntroductionIn previous research, antibacterial photodynamic therapy using lysine-porphyrin conjugate LD4 effectively inactivated methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli; however, it exhibited limited activity against Candida albicans and Mycobacterium tuberculosis.MethodsTo address this limitation, we developed a synergistic antibacterial strategy by combining LD4 with Cu2+ or Zn2+.ResultsSynergy was confirmed via minimum inhibitory concentration and fractional inhibitory concentration index analyses, demonstrating 16- to 64-fold enhanced antibacterial efficacy compared to LD4 alone. Mechanistic studies revealed divergent pathways for LD4 + Cu2+ and LD4 + Zn2+: Zn2+ increased the reactive oxygen species yield and promoted LD4 uptake by pathogens, while LD4 + Cu2+ induced oxidative damage to cell walls and membranes in darkness, with light exposure exacerbating structural damage. Cytotoxicity assessments confirmed low toxicity, with >90% survival of normal cells at bactericidal concentrations. Fluorescence and infrared spectroscopy characterized metal-LD4 complexes, showing stabilization through interactions between amino and pyrrolic imino groups of LD4 and metal ions, which promoted non-radiative transitions and fluorescence quenching. Both combinations caused significant bacterial membrane disruption and growth suppression. Notably, cytotoxicity exhibited a biphasic dose-response linked to metal-LD4 complexation-dependent particle size changes.DiscussionThis study elucidated the enhanced antimicrobial mechanisms and safety of LD4-metal ion combinations. The findings resolve the limitations of LD4 while providing a theoretical framework for developing novel therapies against fungal and mycobacterial infections.https://www.frontiersin.org/articles/10.3389/fphar.2025.1626193/fullantibacterial photodynamic therapylysine-conjugated porphyrin compoundmetal ionssynergistic antibacterial therapyCandida albicansMycobacterium tuberculosis |
| spellingShingle | Xueming Wang Zhonghua Qin Ying Wen Mingxuan Chi Lixia Zhang Junping Wu Tianjun Liu Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis Frontiers in Pharmacology antibacterial photodynamic therapy lysine-conjugated porphyrin compound metal ions synergistic antibacterial therapy Candida albicans Mycobacterium tuberculosis |
| title | Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis |
| title_full | Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis |
| title_fullStr | Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis |
| title_full_unstemmed | Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis |
| title_short | Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination against Candida albicans and Mycobacterium tuberculosis |
| title_sort | synergistic antibacterial photodynamic therapy of lysine porphyrin conjugate and metal ions combination against candida albicans and mycobacterium tuberculosis |
| topic | antibacterial photodynamic therapy lysine-conjugated porphyrin compound metal ions synergistic antibacterial therapy Candida albicans Mycobacterium tuberculosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1626193/full |
| work_keys_str_mv | AT xuemingwang synergisticantibacterialphotodynamictherapyoflysineporphyrinconjugateandmetalionscombinationagainstcandidaalbicansandmycobacteriumtuberculosis AT zhonghuaqin synergisticantibacterialphotodynamictherapyoflysineporphyrinconjugateandmetalionscombinationagainstcandidaalbicansandmycobacteriumtuberculosis AT yingwen synergisticantibacterialphotodynamictherapyoflysineporphyrinconjugateandmetalionscombinationagainstcandidaalbicansandmycobacteriumtuberculosis AT mingxuanchi synergisticantibacterialphotodynamictherapyoflysineporphyrinconjugateandmetalionscombinationagainstcandidaalbicansandmycobacteriumtuberculosis AT lixiazhang synergisticantibacterialphotodynamictherapyoflysineporphyrinconjugateandmetalionscombinationagainstcandidaalbicansandmycobacteriumtuberculosis AT junpingwu synergisticantibacterialphotodynamictherapyoflysineporphyrinconjugateandmetalionscombinationagainstcandidaalbicansandmycobacteriumtuberculosis AT tianjunliu synergisticantibacterialphotodynamictherapyoflysineporphyrinconjugateandmetalionscombinationagainstcandidaalbicansandmycobacteriumtuberculosis |