Antimicrobial Photodynamic therapy enhanced by the peptide aurein 1.2

Abstract

In the past few years, the World Health Organization has been warning that the post-antibiotic era is an increasingly real threat. The rising and disseminated resistance to antibiotics made mandatory the search for new drugs and/or alternative therapies that are able to eliminate resistant microorganisms and impair the development of new forms of resistance. In this context, antimicrobial photodynamic therapy (aPDT) and helical cationic antimicrobial peptides (AMP) are highlighted for the treatment of localized infections. This study aimed to combine the AMP aurein 1.2 to aPDT using Enterococcus faecalis as a model strain. Our results demonstrate that the combination of aPDT with aurein 1.2 proved to be a feasible alternative capable of completely eliminating E. faecalis employing low concentrations of both PS and AMP, in comparison with the individual therapies. Aurein 1.2 is capable of enhancing the aPDT activity whenever mediated by methylene blue or chlorin-e6, but not by curcumin, revealing a PS-dependent mechanism. The combined treatment was also effective against different strains; noteworthy, it completely eliminated a vancomycin-resistant strain of Enterococcus faecium. Our results suggest that this combined protocol must be exploited for clinical applications in localized infections as an alternative to antibiotics.

Rose Bengal-Mediated Photoinactivation of Multidrug Resistant Pseudomonas aeruginosa Is Enhanced in the Presence of Antimicrobial Peptides

“…In the case of another photosensitizer curcumin, the synergistic effect was not observed at all. This proves that the enhanced action of aPDI and AMP was PS-dependent ( de Freitas et al, 2018 ). In our studies, RB proved to be very good PS for combined aPDI and AMP action, whereas it is commonly known that RB itself is not effective against Gram-negative species ( Bezman et al, 1978 ; Schafer et al, 2000 ; Demidova and Hamblin, 2005 ; Wen et al, 2017 ).…”

“…This further means that a PS does not have to be accumulated inside the cells to perform an efficient photodynamic action ( Preuss et al, 2013 ). For example, chlorin-e6 uptake was significantly decreased in the presence of AMP, however, the synergistic action of aPDI and AMP was still observed ( de Freitas et al, 2018 ). Such a characteristic of aPDI is an advantage as it means that bactericidal action can be started from the outside of the cell rather than from the inside where DNA could be affected and potentially mutagenized.…”

“…Such an approach is simpler and also cheaper as the conjugation step can be avoided. There has been only one elegant work done recently on the combination of three types of a photosensitizer, namely curcumin, methylene blue, and chlorin Ce6 with an AMP aurein 1.2, where free, non-conjugated molecules showed excellent activity ( de Freitas et al, 2018 ). In the cited work, the authors focused on Gram-positive species, namely Enterococcus faecium , with an unknown antibiotic resistance pattern.…”

An Insight into Advanced Approaches for Photosensitizer Optimization in Endodontics—A Critical Review

“…Additionally, it was possible to perceive that MB accumulated inside prokaryote cells, while chlorin e 6 attached to the outside of bacterial cells. The studies revealed not only distinct mechanisms of action, but also evidenced the multiple-target nature of the photodynamic effect [100].…”

Hydrogels: soft matters in photomedicine

“…Positively charged molecules, such as the polymixin B nonapeptide, have been used to functionalize PSs for PACT applications by improving their internalization by different strains of Gram-negative bacteria. 78 Chlorin e 6 (56), a chlorophyll-derived tetrapyrrole, combined with the cationic polymer polyethylenimine (PEI) also showed PACT efficiency against some strains of Gram-negative bacteria. 79 Indeed, PSs possessing a positively charged molecular structure, such as tetracationic porphyrins, phthalocyanines and dyes such as toluidine blue O (31) or methylene blue (30), are the most suited to eliminate tough Gram-negative species of bacteria.…”