Evidence map›Paper›PMID 40952433›Full record

ArticleMycopathologia2025

Agricultural SDHIs Induce Azole Resistance in Aspergillus fumigatus via Mitochondrial Sdh1 Suppression.

Heng Zhang, Zhangling Zhu, Mengqi Peng, Sijie Liu, Xiao Gong, Tian Chen, Qingwen Hu, Linyun Li, Zha-Xi Dun-Zhu, Lha-Zom Drol-Ga and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Mycopathologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Heng Zhang *Department of Dermatology, Jingzhou Hospital Affiliated to Yangtze University, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection, Jingzhou, 434100, Hubei Province, China.ORCID http://orcid.org/0009-0002-6618-5311
Zhangling Zhu *Department of Ophthalmology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434100, Hubei Province, China.
Mengqi PengDepartment of Dermatology, Jingzhou Hospital Affiliated to Yangtze University, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection, Jingzhou, 434100, Hubei Province, China.
Sijie LiuDepartment of Dermatology, Jingzhou Hospital Affiliated to Yangtze University, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection, Jingzhou, 434100, Hubei Province, China.
Xiao GongDepartment of Dermatology, Jingzhou Hospital Affiliated to Yangtze University, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection, Jingzhou, 434100, Hubei Province, China.
Tian ChenDepartment of Clinical Medical, Yangtze University, Jingzhou, 434100, Hubei Province, China.
Qingwen HuDepartment of Clinical Medical, Yangtze University, Jingzhou, 434100, Hubei Province, China.
Linyun LiDepartment of Clinical Laboratory, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, 434100, Hubei Province, China.
Zha-Xi Dun-ZhuDepartment of Clinical Medical, The Central Hospital of Jiacha County, Shannan, 856400, Tibet Autonomous Region, China.
Lha-Zom Drol-GaDepartment of Clinical Medical, The Central Hospital of Jiacha County, Shannan, 856400, Tibet Autonomous Region, China.
Yi SunDepartment of Dermatology, Jingzhou Hospital Affiliated to Yangtze University, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection, Jingzhou, 434100, Hubei Province, China. jzzxyysy@163.com.ORCID http://orcid.org/0000-0002-4489-3803

Funding

Jingzhou Science and Technology Plan Project 2024HD34Key Research and Development program of Hubei Province 2024BCB043Yangtze University Science and Technology Aid to Tibet Medical Talent Training Program Project 2023YZ06
6 · The paper itself

Abstract

introductionAspergillus fumigatus poses significant clinical challenges due to its increasing azole resistance. This study investigates the sdh1 gene's role in regulating azole susceptibility, mitochondrial function, and virulence. MATERIALS AND

methodsFungal strains were co-cultured with varying concentrations of succinate dehydrogenase inhibitors (SDHIs). Post-treatment azole minimum inhibitory concentrations (MICs) were determined using broth microdilution method, while succinate dehydrogenase subunit (SDH) expression changes were analyzed via RT-qPCR. Using A. fumigatus MFIG001 as the parental strain, sdh1 knockout mutant (Δsdh1) and complemented strain (Δsdh1::sdh1

resultsExposure to subinhibitory concentrations of SDHIs induced azole resistance in A. fumigatus, with 4.12% of strains exhibiting reduced susceptibility to voriconazole, itraconazole, and posaconazole. RT-qPCR analysis revealed significant downregulation of sdh1 in resistant strains, implicating its role in resistance development. Deletion of sdh1 resulted in an 8- to 16-fold increase in triazole MICs, confirming its role as a negative regulator of azole susceptibility. Phenotypically, the Δsdh1 strain exhibited impaired growth, reduced sporulation, and diminished efficacy of azole treatment in the G. mellonella infection model. Furthermore, Δsdh1 exhibited severe mitochondrial dysfunction, including reduced SDH activity, decreased ATP levels, elevated ROS, and impaired antioxidant defenses. RNA-seq analysis revealed that the deletion of sdh1 upregulated the expression of efflux pump genes (e.g., cdr1B, abcB, mdr4), while Rhodamine 6G efflux assays demonstrated significantly enhanced efflux activity. DISCUSSION: These results identify sdh1 as a critical determinant of azole susceptibility through dual mechanisms: mitochondrial function maintenance and efflux pump regulation. The observed SDHI-induced cross-resistance suggests agricultural fungicides may drive environmental selection of azole-resistant strains. While sdh1 deletion increased drug tolerance through efflux activation, the concurrent mitochondrial damage reduced pathogenic fitness, revealing compensatory evolutionary constraints. This work highlights the need to monitor non-target effects of agricultural SDHIs on clinical antifungal resistance.

Indexed as

Antifungal AgentsAspergillus fumigatusAzolesDrug Resistance, FungalMitochondriaSuccinate DehydrogenaseAnimalsAspergillosisDisease Models, AnimalFungal ProteinsGene Expression ProfilingMicrobial Sensitivity TestsMothsReactive Oxygen SpeciesVirulenceAntifungal AgentsAzolesFungal ProteinsReactive Oxygen SpeciesSuccinate DehydrogenaseAspergillus fumigatusAzole resistanceEfflux pumpssdh1Succinate dehydrogenase

Identifiers

PMID40952433

What Socratic holds

Textmetadata
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Registered trials

None linked

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 Socratic graph.