Evidence map›Paper›PMID 41706153›Full record

ArticleApplied microbiology and biotechnology2026

Nootkatone antifungal activity and calcium signaling-mediated resistance in Aspergillus fumigatus.

Jiadong Xu, Lingyun Song, Yuncan Chen, Jie Tang, Xiangmin Lv, Hongyi Du, Jinxing Song, Jun Tian

Abstract read
In one paragraph

Article in Applied microbiology and biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. International journal of molecular sciences · 2026
    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

8 authors.

Jiadong Xu *China Tobacco Chongqing Industrial Co., Ltd, Chongqing, 406000, China.
Lingyun Song *JSNU-UWEC Joint Laboratory of Jiangsu Province Colleges and Universities, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, China.
Yuncan ChenChina Tobacco Chongqing Industrial Co., Ltd, Chongqing, 406000, China.
Jie TangChina Tobacco Chongqing Industrial Co., Ltd, Chongqing, 406000, China.
Xiangmin LvChina Tobacco Chongqing Industrial Co., Ltd, Chongqing, 406000, China.
Hongyi DuChina Tobacco Chongqing Industrial Co., Ltd, Chongqing, 406000, China.
Jinxing SongJSNU-UWEC Joint Laboratory of Jiangsu Province Colleges and Universities, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, China. zdsongjinxing@jsnu.edu.cn.
Jun TianJSNU-UWEC Joint Laboratory of Jiangsu Province Colleges and Universities, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, China. tj-085@163.com.

Funding

Chongqing China Tobacco Industry Co., Ltd. Research Project HX20230203
6 · The paper itself

Abstract

Tobacco is rich in natural bioactive compounds, yet the antifungal potential of its essential oil remains largely unexplored. In this study, we demonstrate for the first time that tobacco essential oil exhibits significant antifungal activity against the opportunistic human pathogen Aspergillus fumigatus. At high concentrations, the oil effectively inhibits hyphal growth and suppresses conidial production. Chemical profiling identified nootkatone as the principal active compound. Nootkatone exerts a concentration-dependent dual antifungal effect, simultaneously inhibiting hyphal elongation and spore formation. Mechanistic analyses revealed that the calcium signaling pathway, particularly the crzA and cchA genes, plays a central regulatory role in mediating fungal resistance to nootkatone. Deletion of either gene (ΔcrzA or ΔcchA) led to significantly increased sensitivity to nootkatone, highlighting their role in nootkatone stress response. Furthermore, under nootkatone stress, CrzA was found to regulate the expression of multiple efflux pump genes (abcC, abcE, atrA, mdr1, and atrB), uncovering a previously unrecognized link between calcium signaling and nootkatone efflux. In addition to targeting cellular signaling, nootkatone also disrupted fungal cell wall integrity and triggered the release of host immune mediators, suggesting a synergistic antifungal mechanism that combines structural disruption with immune activation. In the Galleria mellonella infection model, nootkatone significantly enhanced host survival and reduced fungal burden. Notably, treatment of ΔcrzA-infected larvae resulted in a 70% survival rate, markedly higher than that observed in wild-type (WT) infections. Moreover, nootkatone retained strong inhibitory activity against itraconazole-resistant isolates, underscoring its potential as a novel, broad-spectrum antifungal agent. KEY POINTS: • Nootkatone inhibits fungal growth-suppresses Aspergillus fumigatus hyphae and spores via dual concentration-dependent action • Targets calcium signaling-key genes (crzA/cchA) regulate resistance; deletion enhances susceptibility and links to efflux pump activation. • Dual antifungal mechanisms and drug resistance overcoming-disrupts cell wall integrity, activates host immunity, and is effective against azole-resistant strains, boosting survival in infection models.

Indexed as

Antifungal AgentsAspergillus fumigatusCalcium SignalingDrug Resistance, FungalPolycyclic SesquiterpenesAnimalsCell WallFungal ProteinsGene DeletionGene Expression Regulation, FungalHyphaeMothsOils, VolatileSpores, FungalAntifungal AgentsCrzA protein, Aspergillus fumigatusFungal ProteinsnootkatoneOils, VolatilePolycyclic SesquiterpenesAntifungal agentsAntifungal resistanceAspergillus fumigatusCalcium signalingNootkatone

Identifiers

PMID41706153
PMCPMC12920313

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.