β-lapachone and α-nor-lapachone modulate Candida albicans viability and virulence factors

Moraes, Daniel Clemente de; Curvelo, José Alexandre Da Rocha; Anjos, Camila A Dos; Moura, Kelly C. G. de; Pinto, Maurício R.; Portela, Maristela Barbosa; Soares, R. Félix

doi:10.1016/j.mycmed.2018.03.004

Cited by 13 publications

(5 citation statements)

References 26 publications

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“…The greater effect of α-nor and β-lap against yeast growth was reported by our group in a previous study using a fluconazole-resistant C. albicans strain [14]. Nevertheless, α-lap and β-nor have also shown antifungal activity against C. albicans, which was not observed in the present study against S. cerevisiae cells.…”

Section: Discussioncontrasting

confidence: 83%

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β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain

et al. 2020

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Objectives The aim of this study was to evaluate the ability of lapachones in disrupting the fungal multidrug resistance (MDR) phenotype, using a model of study which an azole-resistant Saccharomyces cerevisiae mutant strain that overexpresses the ATPbinding cassette (ABC) transporter Pdr5p. Methods The evaluation of the antifungal activity of lapachones and their possible synergism with fluconazole against the mutant S. cerevisiae strain was performed through broth microdilution and spot assays. Reactive oxygen species (ROS) and efflux pump activity were assessed by fluorometry. ATPase activity was evaluated by the Fiske and Subbarow method. The effect of βlapachone on PDR5 mRNA expression was assessed by RT-PCR. The release of hemoglobin was measured to evaluate the hemolytic activity of β-lapachone. Results α-nor-Lapachone and β-lapachone inhibited S. cerevisiae growth at 100 μg/ml. Only β-lapachone enhanced the antifungal activity of fluconazole, and this combined action was inhibited by ascorbic acid. β-Lapachone induced the production of ROS, inhibited Pdr5p-mediated efflux, and impaired Pdr5p ATPase activity. Also, β-lapachone neither affected the expression of PDR5 nor exerted hemolytic activity. Conclusions Data obtained indicate that β-lapachone is able to inhibit the S. cerevisiae efflux pump Pdr5p. Since this transporter is homologous to fungal ABC transporters, further studies employing clinical isolates that overexpress these proteins will be conducted to evaluate the effect of β-lapachone on pathogenic fungi.

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Section: Discussioncontrasting

confidence: 83%

“…In a previous work, our group aimed to study the effect of lapachones on C. albicans virulence factors. It was observed that βlapachone and α-nor-lapachone were able to inhibit C. albicans growth, yeast-to-hyphae transition, biofilm formation, and cell wall mannoprotein expression [14].…”

Section: Introductionmentioning

confidence: 99%

β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain

et al. 2020

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“…These data corroborate the reduction observed in C. albicans biofilm treated with etomidate. Therefore, substances that can affect the potential of C. albicans to promote pathogenesis, and decrease glycoconjugate expression or activity, can be considered to be extremely relevant to improve prognosis [27].…”

Section: Discussionmentioning

confidence: 99%

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Sá

Silva

Neto

et al. 2020

Journal of Medical Microbiology

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This study evaluated the effect of etomidate against biofilms of Candida spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25–500 µg ml−1. Then, an ALS3 adhesive protein from C. albicans was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant C. albicans, C. parapsilosis and C. tropicalis at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of C. albicans. These results revealed that etomidate inhibited the growth of biofilms.

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“…O biofilme é um fator importante que confere proteção mecânica em cepas PRI, demonstrando que o uso da β-lapachona reduz a virulência desta cepa. (MORAES et al, 2018).…”

Section: Formação De Biofilmeunclassified

Ação Antifúngica Da Beta-Lapachona Frente a Cepas Multidrogas Resistentes

Lucas Cavalcanti Fernandes Da Silva,

De Oliveira Barbosa,

Da Silva

et al. 2023

REMS

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O uso excessivo de antimicrobianos nas últimas décadas resultou no aparecimento de cepas multidrogas resistentes (MDR). Infecções causadas por fungos resistentes são um grande problema para a saúde pública, devido à alta mortalidade relacionada a esses casos. A escassez na diversidade de antifúngicos eleva as chances do microrganismo adquirir resistência, bem como a falta de variedade leva ao uso de antimicrobianos de alta toxidade. As principais formas de se escapar da ação farmacológica dos antibióticos são: bomba de efluxo, que diminuem a concentração intracelular da droga e o desenvolvimento de biofilmes que impedem a chegada do agente antifúngico em seu local de ação, conferindo também virulência a cepa. OBJETIVOS: O presente estudo tem em vista assimilar informações sobre o potencial antimicrobiano da beta-lapachona e dissertar suas vantagens contra fungo emergentes. METODOLOGIA: Foram utilizadas as plataformas de pesquisa PubMed, ScienceDirect, Scielo. Utilizou-se dos descritivos “Beta-lapachona” “Biofilmes”,“Mecanismos de resistência”. Os artigos escolhidos língua inglesa entre os anos 2018 e 2022 de publicação. RESULTADOS: Verificou-se o aumento da concentração de Espécies Reativas De O₂ (ROS) (até 5x) na célula, podendo causar danos a estrutura do organismo levando a morte celular. Esta droga também reduziu os níveis de NAD(P)H devido ao estímulo exaustivo do ciclo de redução na mitocôndria. Além de seu uso isolado, a ação conjunta com o fluconazol inibiu o crescimento de cepas resistentes. O efeito sinérgico desta droga proporciona a inibição da bomba de efluxo, permitindo a permanência do antimicrobiano na célula. A atividade da Beta-lapachona contra os biofilmes reduziu a síntese destes (em até 95% em determinadas cepas) e levou a queda no desempenho (88% em fenótipos específicos). CONCLUSÃO: Em suma, podemos inferir que os dados atuais vêm mostrando resultados bastante promissores quanto o possível uso desse agente antimicrobiano na clínica, seja associado a outras drogas ou isoladamente. Ainda pode-se levar em consideração seu uso sanitizante.

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β-lapachone and α-nor-lapachone modulate Candida albicans viability and virulence factors

Cited by 13 publications

References 26 publications

β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain

β-Lapachone enhances the antifungal activity of fluconazole against a Pdr5p-mediated resistant Saccharomyces cerevisiae strain

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Ação Antifúngica Da Beta-Lapachona Frente a Cepas Multidrogas Resistentes

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