Elucidation of the secretory crosstalk between the pathogens Candida albicans and Aspergillus fumigatus via multimodal metabolomics
Abstract
Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) are major opportunistic species, classified by the World Health Organization(WHO) in 2022 as critical priority pathogen due to their high morbidity and mortality rates. Despite the prevalence of Candida-Aspergillus coinfections in organ transplant recipients and patients with hematologic malignancies, mechanisms underlying their biological interplay remain poorly understood. Using a combinatory metabolomics approach of targeted proton Nuclear Magnetic Resonance spectroscopy and untargeted metabolomics by trapped ion mobility spectrometry time-of-flight mass spectrometry, we investigated metabolic interactions between these pathogens and annotated a total of 176 compounds. We highlighted ten A. fumigatus mycotoxins, among them, sphingofungin B and D and spirotryprostatin A, decreased in the presence of C. albicans secretomes, indicating a potential inhibitory effect. Notably, C. albicans cultures exposed to conidia secretome formed a distinct metabolic cluster. In coculture, an inhibition zone with fragmented A. fumigatushyphae was observed, suggesting hyphal damage. Despite this, both species could grow together, highlighting their capacity of cohabitation albeit displaying antagonistic metabolic interactions. The observed inhibition zone and mycotoxin modulation suggest a competitive, yet non-lethal interaction characterized by unique metabolomic chemo-sensing. Importantly, the production of tissue-damaging mycotoxins such as sphingofungin B and D, TR-2 in A. fumigatus- C. albicans coinfection may predispose infected sites to polymicrobial invasion, exacerbating disease severity and persistence, impairing treatment efficacy and worsening patient prognosis.
Keywords
Citation Information
@article{sophietonneau2026,
title={Elucidation of the secretory crosstalk between the pathogens Candida albicans and Aspergillus fumigatus via multimodal metabolomics},
author={Sophie Tonneau and Denis Ispan and Gyuntae Bae and Jannik Sprengel and Frederic Dalle and Nicolas Beziere and Christoph Trautwein},
journal={Research Square},
year={2026},
doi={https://doi.org/10.21203/rs.3.rs-9059703/v1}
}
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