Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, PO Box 486, 31270-901 Belo Horizonte, Minas Gerais, Brazil; Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, United States.
Departamento de Biociências e Diagnóstico Bucal, Instituto de Ciência e Tecnologia, Universidade Estadual Paulista "Júlio de Mesquita Filho", São José dos Campos, São Paulo, Brazil; Postgraduate Program in Nursing, University of Guarulhos, São Paulo, Brazil.
J Mycol Med. 2021 Jun;31(2):101134. doi: 10.1016/j.mycmed.2021.101134. Epub 2021 Apr 6.
Candida albicans is a pathogen equipped with a variety of commensal and virulence traits that help it colonize the microbiota and invade host tissue during infection. In this study, we investigated the potential anticandidal activity of 3-[2-(4-(4-methoxyphenyl)thiazol-2-yl)hydrazino)]butan-1-ol (MT), a thiazolylhydrazone compound synthesized by our group, and identified it as a promising antifungal agent. The activity of MT was evaluated in vitro and in vivo against C. albicans as well as its ability to inhibit virulence factors. For this, the ability of MT to inhibit the adhesion of C. albicans to human buccal epithelial cells and biofilm formation and filamentation was tested. In addition, the potential in vivo activity of MT was evaluated in murine models of oral candidiasis. Our results confirmed the antifungal activity of MT, with a minimal inhibitory concentration range of 0.5-2 µg/mL. Indeed, MT treatment in vitro decreased the expression of C. albicans genes involved in biofilm formation and morphogenesis and encoding hydrolytic enzymes, which was also confirmed through phenotypic observations. In addition, MT promoted a decrease in the colony forming units recovered from the tongues of mice with oral candidiasis. In this work, we present a potent antivirulence compound that shows potential for candidiasis therapy, especially for topical use.
白色念珠菌是一种病原体,具有多种共生和毒力特征,有助于其在感染过程中定植于微生物群并侵袭宿主组织。在这项研究中,我们研究了 3-[2-(4-(4-甲氧基苯基)噻唑-2-基)肼基]-1-丁醇 (MT) 的潜在抗真菌活性,MT 是我们小组合成的一种噻唑基腙化合物,被鉴定为一种有前途的抗真菌剂。我们评估了 MT 在体外和体内对白色念珠菌的活性及其抑制毒力因子的能力。为此,测试了 MT 抑制白色念珠菌与人颊上皮细胞黏附和生物膜形成和丝状形成的能力。此外,还评估了 MT 在口腔念珠菌病小鼠模型中的潜在体内活性。我们的结果证实了 MT 的抗真菌活性,其最小抑制浓度范围为 0.5-2μg/ml。事实上,MT 处理体外降低了参与生物膜形成和形态发生以及编码水解酶的白色念珠菌基因的表达,这也通过表型观察得到了证实。此外,MT 促进了口腔念珠菌病小鼠舌头上回收的菌落形成单位的减少。在这项工作中,我们提出了一种有效的抗毒力化合物,显示出治疗念珠菌病的潜力,特别是用于局部应用。