Valente Michele Ramos, Martins Alcântara Lucas, Cintra Deborah Santos, Mendoza Susana Ruiz, Medeiros Elisa Gonçalves, Gomes Kamilla Xavier, Honorato Leandro, Almeida Marcos de Abreu, Vieira Carmen Baur, Nosanchuk Joshua Daniel, Sgarbi Diana Bridon da Graça, Pinto Marcia Ribeiro, Nimrichter Leonardo, Guimarães Allan Jefferson
Laboratório de Bioquímica e Imunologia das Micoses, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil.
Programa de Pós-Graduação em Microbiologia e Parasitologia Aplicadas, Instituto Biomédico, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil.
Microbiol Spectr. 2025 Feb 4;13(2):e0174624. doi: 10.1128/spectrum.01746-24. Epub 2024 Dec 17.
is an emerging fungal pathogen notable for its resistance to multiple antifungals and ability to survive in various environments. Understanding the interactions between and environmental protozoa, such as could provide insights into fungal adaptability and pathogenicity. Two isolates (MMC1 and MMC2) were co-cultured with to examine interaction dynamics, survival, stress responses, growth, virulence, biofilm formation, and antifungal susceptibility. The association varied with a multiplicity of infection (MOI), with MMC2 exhibiting higher association rates at increased MOI than MMC1. Both isolates survived distinctly within , as the MMC1 showed an initial decline and subsequent increase in viability, while MMC2 maintained higher viability for up to 24 h, decreasing afterward. Both isolates exhibited accelerated growth when recovered from . The MMC2 isolate displayed increased resistance to oxidative, osmotic, and thermal stresses upon interaction with , whereas MMC1 showed limited changes. Exposure to also influenced the expression of virulence factors differently, with MMC1 increasing phospholipase and peptidase, while MMC2 upregulated phytase, esterase, hemolysin, and siderophores. Upon contact with , MMC2 enhanced biofilm formation, unlike MMC1. Both isolates increased ergosterol upon interactions, enhancing susceptibility to amphotericin B. However, both isolates were more tolerant to itraconazole and caspofungin, particularly MMC2, which showed differential expression of ergosterol biosynthesis enzymes and increased cell wall polysaccharides. This study reveals that interactions with modulate physiology and virulence, contributing to its environmental adaptability and resistance to antifungals.
has emerged as a critical public health concern due to its resistance to multiple antifungal drugs and ability to survive on surfaces under harsh conditions, mainly due to biofilm formation. The precise origin of this emerging pathogen still awaits elucidation, but interactions with environmental protozoa may have helped to develop such virulence and resistance traits. In this work, we precisely characterize the interactions of with the free-living amoeba and how these protozoa may alter the fungal behavior in terms of virulence, thermotolerance, biofilm formation capacity, and drug resistance. It may be essential to understand the various interactions could perform in the environment, directly impacting the outcome of human infections under the One Health approach.
是一种新出现的真菌病原体，以其对多种抗真菌药物的耐药性以及在各种环境中生存的能力而闻名。了解其与环境原生动物（如）之间的相互作用，有助于深入了解真菌的适应性和致病性。将两个分离株（MMC1和MMC2）与共同培养，以研究相互作用动态、生存、应激反应、生长、毒力、生物膜形成和抗真菌药敏性。与的关联因感染复数（MOI）而异，MMC2在MOI增加时比MMC1表现出更高的关联率。两个分离株在体内的存活情况明显不同，MMC1的活力最初下降，随后上升，而MMC2在长达24小时内保持较高活力，之后下降。从体内恢复后，两个分离株的生长均加速。与相互作用后，MMC2分离株对氧化、渗透和热应激的抗性增加，而MMC1的变化有限。暴露于也不同程度地影响毒力因子的表达，MMC1增加磷脂酶和肽酶，而MMC2上调植酸酶、酯酶、溶血素和铁载体。与接触后，MMC2增强了生物膜形成，与MMC1不同。相互作用后，两个分离株的麦角固醇均增加，对两性霉素B的敏感性增强。然而，两个分离株对伊曲康唑和卡泊芬净更耐受，尤其是MMC2，其麦角固醇生物合成酶表达不同，细胞壁多糖增加。这项研究表明，与的相互作用调节了的生理和毒力，有助于其环境适应性和抗真菌耐药性。
由于其对多种抗真菌药物的耐药性以及在恶劣条件下在表面生存的能力，主要是由于生物膜形成，已成为一个关键的公共卫生问题。这种新出现病原体的确切起源仍有待阐明，但与环境原生动物的相互作用可能有助于发展出这样的毒力和耐药特性。在这项工作中，我们精确地描述了与自由生活变形虫之间的相互作用，以及这些原生动物如何在毒力、耐热性、生物膜形成能力和耐药性方面改变真菌行为。了解在环境中可能发生的各种相互作用可能至关重要，这直接影响到“同一健康”方法下人类感染的结果。
