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<p><i>Aspergillus fumigatus</i> presents a significant threat to immunocompromised individuals, especially in the context of rising antifungal resistance. In this study, high-resolution transcriptomic profiling was employed to elucidate the molecular mechanism of action of cerium metal–organic framework–functionalized carbon nanotubes (CeMOF@CNT) and its sodium lignosulfonate-functionalized counterpart (SLS-CeMOF@CNT) against <i>Aspergillus fumigatus</i>. The MIC₅₀ values were determined to be 4.24&#xa0;mg/mL for CeMOF@CNT and 3.46&#xa0;mg/mL for SLS-CeMOF@CNT, confirming the enhanced potency of the functionalized formulation. CeMOF@CNT treatment induced a 2.70-fold increase in ATP hydrolysis and a 3.02-fold upregulation of ATPase-coupled transmembrane transporters, leading to energy depletion and ion homeostasis disruption. A robust ROS-mediated stress response was observed, with upregulation of Mn-SOD (3.1-fold) and catalase (2.80-fold), accompanied by downregulation of chitin synthase (− 3.60-fold) and fasciclin domain proteins (− 3.30-fold), indicating compromised cell wall integrity. SLS-CeMOF@CNT demonstrated superior antifungal efficacy, with ATP hydrolysis elevated to 2.89-fold and Mn-SOD expression reaching 3.80-fold, contributing to aggravated mitochondrial dysfunction. Moreover, enrichment of sulfur metabolism (2.91-fold) and amino acid biosynthesis (3.52-fold) pathways suggested elevated metabolic stress under SLS-CeMOF@CNT exposure. Collectively, this study provides the first transcriptomic evidence linking nanocomposite-induced fungal lethality to ATP depletion, oxidative stress, and structural destabilization, highlighting SLS-CeMOF@CNT as a promising antifungal candidate for further investigation in synergistic, biocompatibility, and in vivo efficacy studies.</p> Graphical abstract <p></p>

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Antifungal inbuilt carbon nanotube based redox metal organic framework validated by transcriptomic analysis in Aspergillus fumigatus

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Dilip Kumar Chandra,
  • Awanish Kumar,
  • Chinmaya Mahapatra

摘要

Aspergillus fumigatus presents a significant threat to immunocompromised individuals, especially in the context of rising antifungal resistance. In this study, high-resolution transcriptomic profiling was employed to elucidate the molecular mechanism of action of cerium metal–organic framework–functionalized carbon nanotubes (CeMOF@CNT) and its sodium lignosulfonate-functionalized counterpart (SLS-CeMOF@CNT) against Aspergillus fumigatus. The MIC₅₀ values were determined to be 4.24 mg/mL for CeMOF@CNT and 3.46 mg/mL for SLS-CeMOF@CNT, confirming the enhanced potency of the functionalized formulation. CeMOF@CNT treatment induced a 2.70-fold increase in ATP hydrolysis and a 3.02-fold upregulation of ATPase-coupled transmembrane transporters, leading to energy depletion and ion homeostasis disruption. A robust ROS-mediated stress response was observed, with upregulation of Mn-SOD (3.1-fold) and catalase (2.80-fold), accompanied by downregulation of chitin synthase (− 3.60-fold) and fasciclin domain proteins (− 3.30-fold), indicating compromised cell wall integrity. SLS-CeMOF@CNT demonstrated superior antifungal efficacy, with ATP hydrolysis elevated to 2.89-fold and Mn-SOD expression reaching 3.80-fold, contributing to aggravated mitochondrial dysfunction. Moreover, enrichment of sulfur metabolism (2.91-fold) and amino acid biosynthesis (3.52-fold) pathways suggested elevated metabolic stress under SLS-CeMOF@CNT exposure. Collectively, this study provides the first transcriptomic evidence linking nanocomposite-induced fungal lethality to ATP depletion, oxidative stress, and structural destabilization, highlighting SLS-CeMOF@CNT as a promising antifungal candidate for further investigation in synergistic, biocompatibility, and in vivo efficacy studies.

Graphical abstract