Abstract
Antimicrobial photodynamic therapy (aPDT) is gaining a special importance as an effective approach against multidrug-resistant strains responsible of fatal infections. The addition of potassium iodide (KI), a non-toxic salt, is recognized to increase the aPDT efficiency of some photosensitizers (PSs) on a broad-spectrum of microorganisms. As the reported cases only refer positive aPDT potentiation results, in this work we selected a broad range of porphyrinic and non-porphyrinic PSs in order to gain a more comprehensive knowledge about this aPDT potentiation by KI. For this evaluation were selected a series of meso-tetraarylporphyrins positively charged at meso positions or at β-pyrrolic positions and the non-porphyrinic dyes Methylene blue, Rose Bengal, Toluidine Blue O, Malachite Green and Crystal Violet; the assays were performed using a bioluminescent E. coli strain as a model. The results indicate that KI has also the ability to potentiate the aPDT process mediated by some of the cationic PSs [Tri-Py(+)-Me, Tetra-Py(+)-Me, Form, RB, MB, Mono-Py(+)-Me, β-ImiPhTPP, β-ImiPyTPP, and β-BrImiPyTPP] allowing a drastic reduction of the treatment time as well as of the PS concentration. However, the efficacy of some porphyrinic and non-porphyrinic PSs [Di-Py(+)-Me opp, Di-Py(+)-Me adj, Tetra-Py, TBO, CV, and MG] was not improved by the presence of the coadjuvant. For the PSs tested in this study, the ones capable to decompose the peroxyiodide into iodine (easily detectable by spectroscopy or by the visual appearance of a blue color in the presence of amylose) were the most promising ones to be used in combination with KI. Although these studies confirmed that the generation of 1O2 is an important fact in this process, the PS structure (charge number and charge position), aggregation behavior and affinity for the cell membrane are also important features to be taken in account.
Highlights
Antibiotics are among the most commonly prescribed drugs used in both human medicine and in farm animals, resulting in the selection of multiple drugs resistant (MDR) bacteria (Economou and Gousia, 2015; O’Neill, 2016)
The preparation of the mono-cationic porphyrins β-ImiPhTPP, β-ImiPyTPP, and β-BrImiPyTPP bearing an imidazole ring at the β-pyrrolic position were synthetized according with a procedure developed in our laboratory (Moura et al, 2019), Crystal Violet (CV) was purchased from Merck, Rose Bengal (RB) from Fluka AG, Malachite Green (MG) from Riedel-de-HaënTM, Methylene Blue (MB) and Toluidine Blue O (TBO) from Acros Organics
The PS, TetraPy(+)-Me, was selected to confirm the benefic effect of KI among other inorganic salts (NaI, NaCl, KCl, and NaBr). This well-known tetracationic porphyrin is extensively studied in bacterial photoinactivation processes and is considered an excellent reference when the efficacy of different cationic porphyrins are compared (Alves et al, 2008; Tavares et al, 2011; Simões et al, 2016)
Summary
Antibiotics are among the most commonly prescribed drugs used in both human medicine and in farm animals, resulting in the selection of multiple drugs resistant (MDR) bacteria (Economou and Gousia, 2015; O’Neill, 2016). Infections with resistant bacteria are difficult to treat, causing severe illness and requiring costly and sometimes toxic alternatives, such as antibiotics of last resort. Bacterial strains resistant to these antibiotics have been isolated worldwide (Levine, 2006; Wang et al, 2018). This resistance can result from a chromosomal gene mutation, but comes mainly from horizontal transfer from external gene sources (Chambers and DeLeo, 2009; DeLeo et al, 2010; Gardete and Tomasz, 2014; Gao et al, 2016). Bacteria will inevitably find ways of resisting to the conventional antibiotics, which is why alternative approaches are urgent
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