In vitro effects of the new antifungal compound manogepix (APX001) against the three most clinically relevant species of Sporothrix.

IF 1.9 4区 生物学 Q3 MICROBIOLOGY
Brazilian Journal of Microbiology Pub Date : 2025-09-01 Epub Date: 2025-07-15 DOI:10.1007/s42770-025-01711-z
Fernando Almeida-Silva, Fernanda Praça Nogueira Marques, Pedro Henrique Tenório-Alvarenga, Vanice Rodrigues Poester, Melissa Orzechowski Xavier, Rosely Maria Zancopé-Oliveira, Rodrigo Almeida-Paes
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引用次数: 0

Abstract

Sporotrichosis is an endemic mycosis that pose significant public health challenges, particularly in Brazil, where zoonotic transmission has increased the number of cases in several regions of the country. The disease is caused by Sporothrix genus, with S. brasiliensis, S. schenckii, and S. globosa as the major agents. The currently available therapies may face limitations such as varying cure rates, long and expensive treatment, and adverse effects. Fosmanogepix, a prodrug converted into manogepix within the host, has demonstrated broad-spectrum antifungal activity, including other thermodimorphic fungal species. Thus, this study aimed to evaluate the in vitro antifungal efficacy of manogepix against three clinically relevant Sporothrix species. Minimal inhibitory and fungicidal concentrations were determined against 24 Sporothrix spp. isolates, as well as potential synergism with antifungal drugs, induction of resistance and growth kinetics of the fungus in the presence of the new antifungal drug. Manogepix exhibited fungicidal activity against the three Sporothrix species tested, with minimum inhibitory concentrations (MIC) ranging from 0.06 to 1 µg/ml. Furthermore, manogepix demonstrated a lower geometric mean of MIC values compared to the antifungal drugs and indifferent interactions with itraconazole, terbinafine and amphotericin B. Prolonged exposure to subinhibitory manogepix concentrations did not induce resistance in the tested strains. These findings indicate manogepix as a promising candidate for the treatment of sporotrichosis, offering a potential alternative in cases of resistance or treatment failure with current antifungals. Further studies are needed to confirm this activity in clinical settings, particularly in diverse geographic regions and against a broader range of Sporothrix strains.

新型抗真菌化合物manogepix (APX001)对三种临床最相关的孢子菌的体外作用。
孢子虫病是一种地方性真菌病,对公共卫生构成重大挑战,特别是在巴西,人畜共患传播在该国几个地区增加了病例数。该病由孢子丝菌属引起,以巴西孢子丝菌、申克孢子丝菌和全球孢子丝菌为主要病原。目前可用的治疗方法可能面临诸如治愈率不同、治疗时间长且昂贵以及不良反应等限制。Fosmanogepix是一种在宿主体内转化为manogepix的前药,具有广谱的抗真菌活性,包括其他热形态真菌。因此,本研究旨在评价马诺盖匹对三种临床相关孢子菌的体外抑菌效果。测定了该药物对24株孢子丝菌的最小抑菌和杀真菌浓度,以及与抗真菌药物的潜在协同作用、诱导耐药性和真菌生长动力学。Manogepix对三种孢子菌均有一定的抑菌活性,最低抑菌浓度(MIC)为0.06 ~ 1µg/ml。此外,与抗真菌药物相比,manogepix显示出较低的MIC值几何平均值,并且与伊曲康唑、特比萘芬和两性霉素b的相互作用无关。这些发现表明,manogepix是治疗孢子菌病的有希望的候选者,在现有抗真菌药物耐药或治疗失败的情况下提供了潜在的替代方案。需要进一步的研究来证实临床环境中的这种活性,特别是在不同的地理区域和针对更广泛的孢子丝菌菌株。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Brazilian Journal of Microbiology
Brazilian Journal of Microbiology 生物-微生物学
CiteScore
4.10
自引率
4.50%
发文量
216
审稿时长
1.0 months
期刊介绍: The Brazilian Journal of Microbiology is an international peer reviewed journal that covers a wide-range of research on fundamental and applied aspects of microbiology. The journal considers for publication original research articles, short communications, reviews, and letters to the editor, that may be submitted to the following sections: Biotechnology and Industrial Microbiology, Food Microbiology, Bacterial and Fungal Pathogenesis, Clinical Microbiology, Environmental Microbiology, Veterinary Microbiology, Fungal and Bacterial Physiology, Bacterial, Fungal and Virus Molecular Biology, Education in Microbiology. For more details on each section, please check out the instructions for authors. The journal is the official publication of the Brazilian Society of Microbiology and currently publishes 4 issues per year.
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