Antimicrobial activity of photosensitizers: arrangement in bacterial membrane matters

Abstract

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/cm2 (5.0 ± 0.4 μg/mL for E. coli and 4.9 ± 0.8 μg/mL for A. baumannii) exceeded those for common antibiotics, making it a prospective antimicrobial agent.

Interactions of Co(II)- and Zn(II)porphyrin of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin with DNA in Aqueous Solution and Their Antimicrobial Activities

“…The presence of a restriction enzyme in bacteria could play a vital role in cleaving the phosphodiester bonds of DNA molecules through the formation of hydrogen bonding between the hydrogen atom of water molecules and the oxygen atom of the phosphodiester bonds. Other studies, however, demonstrated that metalloporphyrins might also be used in photodynamic therapy (PDT) as antibacterial agents. − In a PDT system, light excites the porphyrins, which then generate free radicals, particularly reactive oxygen species, that cleave biomolecules, including DNA.…”

“…Other studies, however, demonstrated that metalloporphyrins might also be used in photodynamic therapy (PDT) as antibacterial agents. 50 − 54 In a PDT system, light excites the porphyrins, which then generate free radicals, particularly reactive oxygen species, that cleave biomolecules, including DNA.…”

Photodynamic Action of Curcumin and Methylene Blue against Bacteria and SARS-CoV-2—A Review

“…A series of water-soluble phosphorus(V) porphyrin molecules with OH or ethoxy axial ligands and phenyl/pyridyl peripheral substituents were used as antimicrobial agents in two Gram-negative bacteria models, such as Escherichia coli ( E. coli ) and Acinetobacter baumannii ( A. baumannii ). These porphyrins with an extremely low light dose of 5 J/cm 2 in MIC 50 values fight against COVID-19, based on the molecular interaction between phosphorus(V) porphyrin and bacterial lipid membranes [ 11 ]. The photodynamic therapy with Tetrahydroporphyrin-tetratosylate photodynamic therapy (THPTS) was also used to prevent the infection of COVID-19 with a virus load-reducing effect only at a higher concentration of 3 µM upon near-infrared light irradiation (760 nm, 3.9 or 7.8 J/cm 2 ), which reduced the viral load in vivo, deactivated SARS-CoV-2 [ 12 ].…”