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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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Grizante Bariao, Patricia Helena ; Tonani, Ludmilla ; Pereira Brancini, Guilherme Thomaz ; Nascimento, Erika ; Leite Braga, Gilberto Ubida ; Wainwright, Mark ; von Zeska Kress, Marcia Regina
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES; v. 21, n. 10, p. 12-pg., 2022-07-11.

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)

Processo FAPESP: 20/07546-2 - Estudo da resistência de isolados clínicos de Fusarium spp. à anfotericina B e aos azóis
Beneficiário:Marcia Regina von Zeska Kress
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/25300-8 - O estudo de isolados clínicos fúngicos de diferentes sítios anatômicos e a metagenômica do microbioma do pulmão de pacientes com fibrose cística
Beneficiário:Marcia Regina von Zeska Kress
Modalidade de apoio: Auxílio à Pesquisa - Regular