Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms

IF 7.2 2区医学 Q1 IMMUNOLOGY

Emerging Infectious Diseases Pub Date : 2025-04-22 DOI:10.3201/eid3105.241910

Nissrine Abou-Chakra, Karen Marie Thyssen Astvad, Jan Martinussen, Amalie Sofie Eilsø Munksgaard, Maiken Cavling Arendrup

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Abstract

In 2022, we initiated systematic 5-fluorocytosine susceptibility testing of Candida spp. isolates in Denmark; we observed a bimodal MIC distribution in C. tropicalis, with MICs >16 mg/L in half the isolates. This study investigates the epidemiology and molecular mechanisms of 5-fluorocytosine resistance in C. tropicalis. We analyzed 104 C. tropicalis isolates from 3 time periods, alongside 353 C. albicans and 227 C. glabrata isolates from 2022. We determined MICs using EUCAST E.Def 7.3. Sequencing of FCY2 (purine-cytosine permease), FCY1 (cytosine deaminase), FUR1 (uracil phosphoribosyl transferase), and URA3 (orotidine-5′-phosphate decarboxylase) genes revealed FCY2 alterations—E49X (30/32), Q7X (1/32), and K6NfsX10 (1/32)—in resistant C. tropicalis strains. We found a URA3 alteration, K177E, in both susceptible and resistant strains. Microsatellite genotyping showed that all C. tropicalis isolates with E49X were clonally related. The marked increase in resistance, driven by the clonal spread of E49X, necessitates further research into virulence and environmental factors.

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抗5-氟胞嘧啶热带假丝酵母的指数克隆扩增及其分子机制的新见解

2022年，我们在丹麦启动了念珠菌分离株系统的5-氟胞嘧啶药敏试验；我们观察到热带镰刀菌的MIC呈双峰分布，一半分离株的MIC为16 mg/L。本研究旨在探讨热带棘球绦虫5-氟胞嘧啶抗性的流行病学及分子机制。我们分析了来自3个时间段的104株热带梭菌，以及来自2022年的353株白色梭菌和227株光滑梭菌。我们使用EUCAST E.Def 7.3测定mic。FCY2（嘌呤-胞嘧啶渗透酶）、FCY1（胞嘧啶脱氨酶）、FUR1（尿嘧啶磷酸核糖基转移酶）和URA3（欧罗嘌呤-5′-磷酸脱羧酶）基因测序显示，FCY2基因在耐药的热带衣原体菌株中发生了e49x（30/32）、Q7X（1/32）和K6NfsX10（1/32）的改变。我们在敏感和耐药菌株中均发现了URA3变异K177E。微卫星基因分型结果表明，携带E49X的热带假体分离株均具有克隆亲缘关系。E49X克隆传播导致耐药性显著增加，需要进一步研究毒力和环境因素。

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来源期刊

Emerging Infectious Diseases 医学-传染病学

CiteScore

17.30

自引率

1.70%

发文量

505

审稿时长

1 months

期刊介绍： Emerging Infectious Diseases is a monthly open access journal published by the Centers for Disease Control and Prevention. The primary goal of this peer-reviewed journal is to advance the global recognition of both new and reemerging infectious diseases, while also enhancing our understanding of the underlying factors that contribute to disease emergence, prevention, and elimination. Targeted towards professionals in the field of infectious diseases and related sciences, the journal encourages diverse contributions from experts in academic research, industry, clinical practice, public health, as well as specialists in economics, social sciences, and other relevant disciplines. By fostering a collaborative approach, Emerging Infectious Diseases aims to facilitate interdisciplinary dialogue and address the multifaceted challenges posed by infectious diseases.