Lung surfactant negatively affects the photodynamic inactivation of bacteria—in vitro and molecular dynamic simulation analyses

• Published in: Proceedings of the National Academy of Sciences - PNAS 2022-06, Vol.119 (25), p.1-9
• Main Authors: Kassab, Giulia, Tovar, Johan Sebastian Diaz, Souza, Lucas Miguel Pereira, Costa, Rayla Kelly Magalhães, Silva, Rudielson Santos, Pimentel, André Silva, Kurachi, Cristina, Bagnato, Vanderlei Salvador
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Bacteria; Bacteria - drug effects; Biological Sciences; Biomolecules; Fluorescence; In vivo methods and tests; Inactivation; Indocyanine Green - pharmacology; Lung - microbiology; Lungs; Methylene blue; Molecular dynamics; Molecular Dynamics Simulation; Phospholipids; Photobleaching; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - pharmacology; Physical Sciences; Pneumonia; Protoporphyrin; Protoporphyrin IX; Simulation; Singlet oxygen; Streptococcus infections; Surface-Active Agents - metabolism; Surfactants
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2123564119

In the context of the rapid increase of antibiotic-resistant infections, in particular of pneumonia, antimicrobial photodynamic therapy (aPDT), the microbiological application of photodynamic therapy (PDT), comes in as a promising treatment alternative since the induced damage and resultant death are not dependent on a specific biomolecule or cellular pathway. The applicability of aPDT using the photosensitizer indocyanine green with infrared light has been successfully demonstrated for different bacterial agents in vitro, and the combination of pulmonary delivery using nebulization and external light activation has been shown to be feasible. However, there has been little progress in obtaining sufficient in vivo efficacy results. This study reports the lung surfactant as a significant suppressor of aPDT in the lungs. In vitro, the clinical surfactant Survanta® reduced the aPDT effect of indocyanine green, Photodithazine®, bacteriochlorintrizma, and protoporphyrin IX against Streptococcus pneumoniae. The absorbance and fluorescence spectra, as well as the photobleaching profile, suggested that the decrease in efficacy is not a result of singlet oxygen quenching, while a molecular dynamics simulation showed an affinity for the polar head groups of the surfactant phospholipids that likely impacts uptake of the photosensitizers by the bacteria. Methylene blue is the exception, likely because its high water solubility confers a higher mobility when interacting with the surfactant layer.We propose that the interaction between lung surfactant and photosensitizer must be taken into account when developing pulmonary aPDT protocols.