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使用模型对抗真菌药物敏感性在生存方面的表型影响及多变量评估

Phenotypic Impact and Multivariable Assessment of Antifungal Susceptibility in Survival Using a Model.

作者信息

Alvarruiz Jorge, Ruiz-Gaitán Alba Cecilia, Cabanero-Navalon Marta Dafne, Pemán Javier, Blanes-Hernández Rosa, de Cossio Santiago, Garcia-Bustos Victor

机构信息

Department of Internal Medicine, University and Polytechnic Hospital La Fe, 46026 Valencia, Spain.

Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain.

出版信息

J Fungi (Basel). 2025 May 24;11(6):406. doi: 10.3390/jof11060406.

DOI:10.3390/jof11060406
PMID:40558919
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12193718/
Abstract

The novel pathogen has rapidly become a major health threat due to its high virulence, resistance to multiple antifungal agents, and remarkable environmental persistence. This study evaluated the influence of phenotypic traits and antifungal minimum inhibitory concentrations (MICs) on virulence using a infection model. Ten clinical strains, categorized as aggregative or non-aggregative, were analyzed for antifungal susceptibility and survival outcomes. All strains exhibited fluconazole resistance, with variable susceptibilities to other antifungals. Survival analysis revealed that the non-aggregative phenotype was independently associated with reduced survival in (HR = 2.418, = 0.015), while antifungal MICs and invasive origin were not significant independent predictors of mortality in an elastic net-adjusted multivariable model. Strong correlations were observed between certain antifungal MICs, suggesting potential cross-resistance patterns; however, no independent association with virulence was identified. These results suggest that possesses not only an enhanced ability to develop antifungal resistance but also the capacity to do so without incurring fitness costs that could attenuate its virulence.

摘要

这种新型病原体因其高毒力、对多种抗真菌药物的耐药性以及在环境中显著的持久性,迅速成为主要的健康威胁。本研究使用感染模型评估了表型特征和抗真菌最低抑菌浓度(MICs)对毒力的影响。对10株分为聚集型或非聚集型的临床菌株进行了抗真菌药敏试验和生存结果分析。所有菌株均表现出对氟康唑耐药,对其他抗真菌药物的敏感性各不相同。生存分析显示,非聚集型表型与感染中生存率降低独立相关(HR = 2.418,P = 0.015),而在弹性网络调整的多变量模型中,抗真菌MICs和侵袭来源并非死亡率的显著独立预测因素。在某些抗真菌MICs之间观察到强相关性,提示潜在的交叉耐药模式;然而,未发现与毒力有独立关联。这些结果表明,该病原体不仅具有增强的产生抗真菌耐药性的能力,而且能够在不产生可能削弱其毒力的适应性代价的情况下产生耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e05/12193718/36e9a68d9b74/jof-11-00406-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e05/12193718/627d6ef6d5e1/jof-11-00406-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e05/12193718/36e9a68d9b74/jof-11-00406-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e05/12193718/627d6ef6d5e1/jof-11-00406-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e05/12193718/36e9a68d9b74/jof-11-00406-g002.jpg

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本文引用的文献

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The multidrug-resistant complex and phylogenetic related species: Insights into antifungal resistance mechanisms.多重耐药复合体及系统发育相关物种:对抗真菌耐药机制的见解
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Do morphogenetic switching and intraspecies variation enhance virulence of Candida auris?
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Ume6-dependent pathways of morphogenesis and biofilm formation in .Ume6 依赖途径在 …… 的形态发生和生物膜形成中的作用。
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Candida auris undergoes adhesin-dependent and -independent cellular aggregation.耳念珠菌经历依赖黏附素和不依赖黏附素的细胞聚集。
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