Rollin-Pinheiro Rodrigo, de Moraes Daniel Clemente, Bayona-Pacheco Brayan, Curvelo Jose Alexandre da Rocha, Dos Santos-Freitas Giulia Maria Pires, Xisto Mariana Ingrid Dutra da Silva, Borba-Santos Luana Pereira, Rozental Sonia, Ferreira-Pereira Antonio, Barreto-Bergter Eliana
Laboratório de Química Biológica de Microrganismos, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil.
Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil.
J Fungi (Basel). 2023 Nov 17;9(11):1115. doi: 10.3390/jof9111115.
species are one of the most concerning causative agents of fungal infections in humans. The treatment of invasive infections is based on the use of fluconazole, but the emergence of resistant isolates has been an increasing concern which has led to the study of alternative drugs with antifungal activity. Sphingolipids have been considered a promising target due to their roles in fungal growth and virulence. Inhibitors of the sphingolipid biosynthetic pathway have been described to display antifungal properties, such as myriocin and aureobasidin A, which are active against resistant isolates. In the present study, aureobasidin A did not display antibiofilm activity nor synergism with amphotericin B, but its combination with fluconazole was effective against biofilms and protected the host in an in vivo infection model. Alterations in treated cells revealed increased oxidative stress, reduced mitochondrial membrane potential and chitin content, as well as altered morphology, enhanced DNA leakage and a greater susceptibility to sodium dodecyl sulphate (SDS). In addition, it seems to inhibit the efflux pump CaCdr2p. All these data contribute to elucidating the role of aureobasidin A on fungal cells, especially evidencing its promising use in clinical resistant isolates of species.
[某种真菌名称]是人类真菌感染中最令人担忧的病原体之一。侵袭性感染的治疗基于氟康唑的使用，但耐药菌株的出现日益受到关注，这促使人们研究具有抗真菌活性的替代药物。鞘脂因其在真菌生长和毒力中的作用而被认为是一个有前景的靶点。鞘脂生物合成途径的抑制剂已被描述具有抗真菌特性，如嗜热栖热放线菌素和金担子素A，它们对耐药菌株具有活性。在本研究中，金担子素A既不显示抗生物膜活性，也不与两性霉素B产生协同作用，但其与氟康唑的组合对生物膜有效，并在体内感染模型中保护宿主。处理后的细胞发生了变化，表现为氧化应激增加、线粒体膜电位降低、几丁质含量减少，以及形态改变、DNA泄漏增加和对十二烷基硫酸钠（SDS）的敏感性增强。此外，它似乎抑制了外排泵CaCdr2p。所有这些数据都有助于阐明金担子素A对真菌细胞的作用，特别是证明其在[某种真菌名称]临床耐药菌株中的潜在应用价值。
