Miguel Camila Botelho, Vilela Geovana Pina, Almeida Lara Mamede, Moreira Mariane Andrade, Silva Glicélia Pereira, Miguel-Neto Jamil, Martins-de-Abreu Melissa Carvalho, Agostinho Ferdinando, Lazo-Chica Javier Emilio, Cardoso Mariana Santos, Soares Siomar de Castro, Góes-Neto Aristóteles, Rodrigues Wellington Francisco
Multidisciplinary Laboratory of Scientific Evidence, University Center of Mineiros (Unifimes), Mineiros 75833-130, GO, Brazil.
Postgraduate Program in Tropical Medicine and Infectious Diseases, Federal University of the Triângulo Mineiro-UFTM, Uberaba 38025-180, MG, Brazil.
J Fungi (Basel). 2025 Mar 12;11(3):215. doi: 10.3390/jof11030215.
is a life-threatening fungal pathogen that primarily affects immunocompromised individuals. While antiretroviral therapy has reduced incidence in developed nations, fluconazole-resistant strains and virulent environmental isolates continue to pose challenges, especially because they have many mechanisms of adaptability, supporting their survival. This study explores the phenetic and metabolomic adaptations of in clinical and environmental contexts to understand the factors influencing pathogenicity and resistance.
An in silico observational study was conducted with 16 isolates (6 clinical, 9 environmental, and 1 reference) from the NCBI database. Molecular phenetic analysis used MEGA version 11.0.13 and focused on efflux pump protein sequences. Molecular phenetic relationships were assessed via the UPGMA clustering method with 1000 bootstrap replicates. The enzymatic profiling of glycolytic pathways was conducted with dbCAN, and metabolomic pathway enrichment analysis was performed in MetaboAnalyst 6.0 using the KEGG pathway database.
Molecular phenetic analysis revealed distinct clustering patterns among isolates, reflecting adaptations associated with clinical and environmental niches. Clinical isolates demonstrated enriched sulfur metabolism and glutathione pathways, likely adaptations to oxidative stress in host environments, while environmental isolates favored methane and glyoxylate pathways, suggesting adaptations for survival in carbon-rich environments.
Significant phenetic and metabolomic distinctions between isolates reveal adaptive strategies for enhancing virulence and antifungal resistance, highlighting potential therapeutic targets.
是一种危及生命的真菌病原体，主要影响免疫功能低下的个体。虽然抗逆转录病毒疗法在发达国家降低了发病率，但耐氟康唑菌株和毒性环境分离株仍然构成挑战，特别是因为它们有许多适应机制来支持其生存。本研究探讨了在临床和环境背景下的表型和代谢组学适应性，以了解影响致病性和耐药性的因素。
对来自NCBI数据库的16株分离株（6株临床分离株、9株环境分离株和1株参考株）进行了计算机模拟观察研究。分子表型分析使用MEGA 11.0.13版本，重点关注外排泵蛋白序列。通过具有1000次重复抽样的UPGMA聚类方法评估分子表型关系。使用dbCAN对糖酵解途径进行酶谱分析，并在MetaboAnalyst 6.0中使用KEGG途径数据库进行代谢组学途径富集分析。
分子表型分析揭示了分离株之间不同的聚类模式，反映了与临床和环境生态位相关的适应性。临床分离株表现出丰富的硫代谢和谷胱甘肽途径，可能是对宿主环境中氧化应激的适应，而环境分离株则倾向于甲烷和乙醛酸途径，表明是对富碳环境中生存的适应。
分离株之间显著的表型和代谢组学差异揭示了增强毒力和抗真菌耐药性的适应策略，突出了潜在的治疗靶点。
