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6. Novel Type of Water-Soluble Photosensitizer from Trichoderma reeseifor Photodynamic Inactivation of Gram-Positive Bacteria

Author

Yang, Zihuayuan, Qiao, Ying, Li, Junying, Wu, Fu-Gen, and Lin, Fengming

Abstract

Antimicrobial photodynamic therapy (APDT) is a promising alternative to traditional antibiotics for the treatment of bacterial infections, which inactivates a broad spectrum of bacteria. However, many traditional photosensitizers (PSs) are hydrophobic with poor water solubility and easy aggregation. On the other hand, some light sources such as ultraviolet (UV) have poor penetration and high cytotoxicity. Both issues lead to undesired photodynamic therapy efficacy. To overcome these issues, we develop a novel water-soluble natural PS (sorbicillinoids) obtained by microbial fermentation using recombinant filamentous fungus Trichoderma reesei. Sorbicillinoids could effectively generate singlet oxygen (1O2) under UV light irradiation and ultimately display photoinactivation activity on Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis,and Micrococcus luteusbut not Gram-negative ones such as Escherichia coliand Proteus vulgaris. Sorbicillinoids were found to enter S. aureusbut not E. coli. S. aureustreated with sorbicillinoids and UV light displayed high levels of intracellular reactive oxygen species (ROS), notable DNA photocleavage, and compromised cell semipermeability without overt cell membrane disruption, none of which was found in the treated E. coli. All these contribute to the sorbicillinoid-based photoinactivation of Gram-positive bacteria. Moreover, the dark toxicity and phototoxicity on mammalian cells or hemolysis activity of sorbicillinoids is negligible, showing its excellent biocompatibility. This study expands the utilization of UV light for surface sterilization to disinfection in solution. Therefore, sorbicillinoids, a type of secondary metabolite from fungus, have a promising future as a new PS for APDT using a nontoxic dose of UV irradiation.

Published
2020
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18. Molecular Interactions between Amantadine and ModelCell Membranes.

Author

Wu, Fu-Gen, Yang, Pei, Zhang, Chi, Li, Bolin, Han, Xiaofeng, Song, Minghu, and Chen, Zhan

Subjects
*MOLECULAR interactions, *AMANTADINE, *CELL membranes, *PHOTON upconversion, *VIBRATIONAL spectra, *BILAYER lipid membranes
Abstract

Sumfrequency generation (SFG) vibrational spectroscopy was appliedto study molecular interactions between amantadine and substrate supportedlipid bilayers serving as model cell membranes. Both isotopicallyasymmetric and symmetric lipid bilayers were used in the research.SFG results elucidated how the water-soluble drug, amantadine, influencedthe packing state of each leaflet of a lipid bilayer and how the drugsaffected the lipid flip-flop process. It is difficult to achieve suchdetailed molecular-level information using other analytical techniques.Especially, from the flip-flop rate change of isotopically asymmetriclipid bilayer induced by amantadine, important information on thedrug–membrane interaction mechanism can be derived. The resultsshow that amantadine can be associated with zwitterionic PC bilayersbut has a negligible influence on the flip-flop behavior of PC moleculesunless at high concentrations. Different effects of amantadine onthe lipid bilayer were observed for the negatively charged DPPG bilayer;low concentration amantadine (e.g., 0.20 mM) in the subphase couldimmediately disturb the outer lipid leaflet and then the lipid associatedamantadine molecules gradually reorganize to cause the outer leafletto return to the original orderly packed state. Higher concentrationamantadine (e.g., 5.0 mM) immediately disordered the packing stateof the outer lipid leaflet. For both the high and low concentrationcases, amantadine molecules only bind to the outer PG leaflet andcannot translocate to the inner layer. The presence of amantadinewithin the negatively charged lipid layers has certain implicationsfor using liposomes as drug delivery carriers for amantadine. Besides,by using PC or PG bilayers with both leaflets deuterated, we wereable to examine how amantadine is distributed and/or oriented withinthe lipid bilayer. The present work demonstrates that SFG resultscan provide an in-depth understanding of the molecular mechanismsof interactions between water-soluble drugs and model cell membranes. [ABSTRACT FROM AUTHOR]

Published
2014
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