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Grizante Barião, PH, Tonani, L, Brancini, GTP, Nascimento, E, Braga, GÚL, Wainwright, M and von Zeska Kress, MR (2022) In vitro and in vivo photodynamic efficacies of novel and conventional phenothiazinium photosensitizers against multidrug-resistant Candida auris. Photochemical and Photobiological Sciences. ISSN 1474-905X
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In vitro and in vivo photodynamic efficacies of novel and conventional phenothiazinium photo- 1.pdf - Accepted Version Download (1MB) | Preview |
Abstract
The fast-emerging and multidrug-resistant Candida auris is the first fungal pathogen to be considered a threat to global public health. Thus, there is a high unmet medical need to develop new therapeutic strategies to control this species. Antimicrobial photodynamic therapy (APDT) is a promising alternative that simultaneously targets and damages numerous microbial biomolecules. Here, we investigated the in vitro and in vivo effects of APDT with four phenothiazinium photosensitizers: (i) methylene blue (MB), (ii) toluidine blue (TBO), and two MB derivatives, (iii) new methylene blue (NMBN) and (iv) the pentacyclic derivative S137, against C.auris. To measure the in vitro efficacy of each PS, minimal inhibitory concentrations (MICs) and survival fraction were determined. Also, the efficiency of APDT was evaluated in vivo with the Galleria mellonella insect model for infection and treatment. Although the C. auris strain used in our study was shown to be resistant to the most-commonly used clinical antifungals, it could not withstand the damages imposed by APDT with any of the four photosensitizers. However, for the in vivo model, only APDT performed with S137 allowed survival of infected G.mellonella larvae. Our results show that structural and chemical properties of the photosensitizers play a major role on the outcomes of in vivo APDT and underscore the need to synthesize and develop novel photosensitizing molecules against multidrug-resistant microorganisms. Graphical abstract: [Figure not available: see fulltext.].
| Item Type: | Article |
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| Additional Information: | This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s43630-022-00258-4 |
| Uncontrolled Keywords: | Antimicrobial photodynamic therapy; Candida auris; Galleria mellonella; Multidrug-resistance; Phenothiazinium photosensitizers; 0299 Other Physical Sciences; 0306 Physical Chemistry (incl. Structural); 0601 Biochemistry and Cell Biology; Organic Chemistry |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Springer |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 23 Aug 2022 11:14 |
| Last Modified: | 11 Jul 2023 00:50 |
| DOI or ID number: | 10.1007/s43630-022-00258-4 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/17258 |
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