期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2023.1192794
关键词
photosensitizer; antimicrobial photodynamic therapy; lipid membrane; antibiotic; molecular dynamics simulation; Echerichia coil; Acinetobacter baumanii; membrane potentials
A comprehensive tool was developed to predict and assess the photodynamic efficacy of photosensitizers in antibacterial photodynamic therapy. A new photosensitizer molecule with a high potential antimicrobial activity was discovered, showing higher minimum inhibitory concentration values for E. coli and A. baumannii compared to common antibiotics.
Porphyrins are well-known photosensitizers (PSs) for antibacterial photodynamic therapy (aPDT), which is still an underestimated antibiotic-free method to kill bacteria, viruses, and fungi. In the present work, we developed a comprehensive tool for predicting the structure and assessment of the photodynamic efficacy of PS molecules for their application in aPDT. We checked it on a series of water-soluble phosphorus(V) porphyrin molecules with OH or ethoxy axial ligands and phenyl/pyridyl peripheral substituents. First, we used biophysical approaches to show the effect of PSs on membrane structure and their photodynamic activity in the lipid environment. Second, we developed a force field for studying phosphorus(V) porphyrins and performed all-atom molecular dynamics simulations of their interactions with bacterial lipid membranes. Finally, we obtained the structure-activity relationship for the antimicrobial activity of PSs and tested our predictions on two models of Gram-negative bacteria, Escherichia coli and Acinetobacter baumannii. Our approach allowed us to propose a new PS molecule, whose MIC50 values after an extremely low light dose of 5 J/cm(2) (5.0 +/- 0.4 mu g/mL for E. coli and 4.9 +/- 0.8 mu g/mL for A. baumannii) exceeded those for common antibiotics, making it a prospective antimicrobial agent.
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