2026-08-15T11:34:46Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/276452026-08-15T00:15:50Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud author Alharthi, Reem author Sueiro-Olivares, Monica author Storer, Isabelle author Bin Shuraym, Hajer author Scott, Jennifer author Al-Shidhani, Reem author Fortune-Grant, Rachael author Bignell, Elaine author Tabernero, Lydia author Bromley, Michael author Zhao, Can author Amich, Jorge funder Agencia Estatal de Investigación (España) funder Wellcome Trust 2026-08-14T11:36:54Z 2026-08-14T11:36:54Z 2025-12 Alharthi, R., Sueiro-Olivares, M., Storer, I., Bin Shuraym, H., Scott, J., Al-Shidhani, R., … Amich, J. (2025). The sulfur-related metabolic status of Aspergillus fumigatus during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target. Virulence, 16(1). https://doi.org/10.1080/21505594.2024.2449075. 10.1080/21505594.2024.2449075 Virulence 39825596 https://hdl.handle.net/20.500.12105/27645 Sulfur metabolism is an essential aspect of fungal physiology and pathogenicity. Fungal sulfur metabolism comprises anabolic and catabolic routes that are not well conserved in mammals, therefore is considered a promising source of prospective novel antifungal targets. To gain insight into sulfur-related metabolism during infection, we used a NanoString custom nCounter-TagSet and compared the expression of 68 key metabolic genes in different murine models of invasive pulmonary aspergillosis, at 3 time-points, and under a variety of conditions. We identified a set of 15 genes that were consistently expressed at higher levels than , suggesting that they may be particularly relevant for intrapulmonary growth and thus constitute promising drug targets. Indeed, the role of 5 of the 15 genes has previously been empirically validated, supporting the likelihood that the remaining candidates are relevant. In addition, the analysis of gene expression dynamics at early (16 h), mid (24 h), and late (72 h) time-points uncovered potential disease initiation and progression factors. We further characterized one of the identified genes, encoding the cytosolic serine hydroxymethyltransferase ShmB, and demonstrated that it is an essential gene of , also required for virulence in a murine model of established pulmonary infection. We further showed that the structure of the ligand-binding pocket of the fungal enzyme differs significantly from its human counterpart, suggesting that specific inhibitors can be designed. Therefore, transcriptomics is a powerful tool for identifying genes crucial for fungal pathogenicity that may encode promising antifungal target candidates. eng Aspergillus fumigatus Antifungal targets Fungal virulence Hydroxymethyltransferase In vivo transcriptomics Sulfur metabolism The sulfur-related metabolic status of during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target. research article 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 URL https://repisalud.isciii.es/bitstreams/2d1ad1c8-d3dd-4783-ae1a-054aab7eb9a5/download File MD5 ef73184036cdb964ae93266c56aeca73 7464654 application/pdf Sulfur-relatedMetabolicStatusAspergillusFumigatus_2025.pdf URL https://repisalud.isciii.es/bitstreams/19ee10f3-4fe5-42e3-adb6-678d249e5841/download File MD5 100b5048054322d7e67f1d1e3c43d542 50305469 application/zip Supplementary_Sulfur-relatedMetabolicStatusAspergillusFumigatus_2025.zip