Evidence map›Paper›PMID 40424325›Full record

ArticlePLoS pathogens2025

Adaptive morphological changes link to poor clinical outcomes by conferring echinocandin tolerance in Candida tropicalis.

Yongqin Wu, Yun Zou, Yuanyuan Dai, Huaiwei Lu, Wei Zhang, Wenjiao Chang, Ying Wang, Zhengchao Nie, Yuanyuan Wang, Xiaohua Jiang

Erratum issuedAbstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Yongqin WuDepartment of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.ORCID 0000-0002-8393-0259
Yun ZouUnit of Pathogenic Fungal Infection & Host Immunity, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
Yuanyuan DaiDepartment of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Huaiwei LuDepartment of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Wei ZhangHefei Center for Disease Control and Prevention, Hefei, Anhui, China.
Wenjiao ChangDepartment of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Ying WangDepartment of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Zhengchao NieDepartment of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Yuanyuan WangThe Center for Microbes, Development, and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China.
Xiaohua JiangCenter for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

Funding

National Natural Science Foundation of China
6 · The paper itself

Abstract

Antibiotic tolerance, by which susceptible bacteria survive at high bactericide doses, is known to cause treatment failure in clinical practice. However, the impact of antifungal tolerance on clinical outcomes remains poorly understood. Here, we observed that candidemia cases caused by echinocandin-tolerant Candida tropicalis exhibited higher mortality rates during caspofungin treatment by conducting a comprehensive seven-year retrospective analysis. C. tropicalis develops tolerance to caspofungin by forming multicellular aggregates, a process linked to defects in cell division, both in vitro and in vivo. Our omics-based profiling results reveal that C. tropicalis develops tolerance through the intricate modulation of cell wall integrity and cell division pathways, particularly through the activation of chitin synthesis and the downregulation of cell division-related genes. The overexpression of cell division-related factor Ace2 can suppress the tolerance of C. tropicalis to caspofungin by delaying the formation of multicellular aggregates. Moreover, calcineurin inhibitors can suppress the tolerance of C. tropicalis by disrupting these adaptive molecular changes, thereby significantly enhancing the antifungal efficacy of caspofungin in a Galleria mellonella model. Collectively, our findings provide evidence that C. tropicalis acquires echinocandin tolerance through morphological alterations, and that inhibiting calcineurin may be a promising method to reduce this tolerance.

Indexed as

Antifungal AgentsCandida tropicalisCandidemiaCandidiasisCaspofunginDrug Resistance, FungalEchinocandinsAnimalsHumansMicrobial Sensitivity TestsRetrospective StudiesAntifungal AgentsCaspofunginEchinocandins

Identifiers

PMID40424325
PMCPMC12140413

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.