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In vitro and in vivo photodynamic efficacies of novel and conventional phenothiazinium photosensitizers against multidrug-resistant Candida auris

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Author(s):
Grizante Bariao, Patricia Helena ; Tonani, Ludmilla ; Pereira Brancini, Guilherme Thomaz ; Nascimento, Erika ; Leite Braga, Gilberto Ubida ; Wainwright, Mark ; von Zeska Kress, Marcia Regina
Total Authors: 7
Document type: Journal article
Source: PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES; v. 21, n. 10, p. 12-pg., 2022-07-11.
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. [GRAPHICS] . (AU)

FAPESP's process: 20/07546-2 - Resistance study of Fusarium spp. clinical isolates to amphotericin B and azoles
Grantee:Marcia Regina von Zeska Kress
Support Opportunities: Regular Research Grants
FAPESP's process: 17/25300-8 - Study of fungal clinical isolates from different anatomical sites and metagenomic of the lung microbiome of patients with cystic fibrosis
Grantee:Marcia Regina von Zeska Kress
Support Opportunities: Regular Research Grants