孢子丝菌病,在拉丁美洲最常见的皮肤真菌病,是由孢子丝菌临床进化枝引起的,包括巴西孢子丝菌和严格的申克孢子丝菌。由于其在巴西的人畜共患传播,巴西链球菌对人类和家畜的健康构成重大威胁。伊曲康唑,特比萘芬,两性霉素B是治疗孢子丝菌病最常用的抗真菌药。然而,巴西链球菌和申克链球菌的许多菌株对这些药物表现出抗性,强调寻找新的治疗选择的重要性。这里,我们证明了milteforan,一种针对利什曼病的商业兽医产品,其活性成分是米替福辛,是治疗孢子丝菌病的一种可能的治疗方法,如通过其对巴西链球菌和申克链球菌的不同菌株的体外杀菌活性所观察到的。荧光米替福辛定位于孢子丝菌细胞膜和线粒体,并通过增加的透化作用导致细胞死亡。Milteforan降低了A549肺细胞和骨髓来源的巨噬细胞中的巴西链球菌真菌负荷,并且还通过降低TNF-α而具有免疫调节作用,IL-6和IL-10的产生。我们的结果表明,milteforan可能是治疗猫孢子丝菌病的替代方法。
目的:孢子丝菌病是由不同种类的孢子丝菌引起的拉丁美洲地方病。这种真菌可以感染家畜,主要是猫,最后是狗,和人类一样。很少有药物可以治疗这种疾病,例如伊曲康唑,特比萘芬,两性霉素B,但是在过去的几年里,对这些药物的抵抗力上升了。治疗孢子丝菌病的替代新治疗选择是必不可少的。这里,我们提议milteforan,一种针对利什曼病的商业兽医产品,其活性成分是米替福辛,作为治疗孢子丝菌病的一种可能的治疗方法。Milteforan降低了人和小鼠细胞中巴西链球菌的真菌负担,并通过减少几种细胞因子的产生而具有免疫调节作用。
Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. Due to its zoonotic transmission in Brazil, S. brasiliensis represents a significant health threat to humans and domestic animals. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains of S. brasiliensis and S. schenckii have shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activity in vitro against different strains of S. brasiliensis and S. schenckii. Fluorescent miltefosine localizes to the Sporothrix cell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreases S. brasiliensis fungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-α, IL-6, and IL-10 production. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis.
OBJECTIVE: Sporotrichosis is an endemic disease in Latin America caused by different species of Sporothrix. This fungus can infect domestic animals, mainly cats and eventually dogs, as well as humans. Few drugs are available to treat this disease, such as itraconazole, terbinafine, and amphotericin B, but resistance to these agents has risen in the last few years. Alternative new therapeutic options to treat sporotrichosis are essential. Here, we propose milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, as a possible therapeutic alternative for treating sporotrichosis. Milteforan decreases S. brasiliensis fungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production.