Scholarlink

<p>Invasive pulmonary mucormycosis caused by <i>Rhizopus microsporus</i> is often fatal, yet analytical tools to monitor fungal burden and host responses in vivo remain limited. We developed a multimodal infection metallomics workflow combining ⁶⁸Ga-desferrioxamine B PET/CT, high-resolution MALDI mass spectrometry imaging (MALDI-MSI), and targeted LC-MS to map fungal siderophore production and host tissue remodeling in a neutropenic rat model and in human samples. ⁶⁸Ga-desferrioxamine B was rapidly taken up by <i>R. microsporus </i>in vitro and accumulated in infected lungs in vivo. MALDI-MSI visualized rhizoferrin (m/z 435.1259, [M−H]⁻) and homorhizoferrin (m/z 449.1420, [M−H]⁻) confined to hyphal foci and absent from control lungs, whereas heme b was depleted and spatially segregated. Neutrophil α-defensins (RatNP-2/3/4) increased 14–60-fold and formed halos around lesions, showing an inverse trend with siderophore abundance. Lipid MSI revealed remodeling of anionic surfactant lipids, with depletion of short-chain phosphatidylglycerols and phosphatidic acid–derived species and accumulation of long-chain polyunsaturated phosphatidylglycerols and phosphatidylinositols in infected regions. Targeted LC-MS of serial urine showed that rhizoferrin and homorhizoferrin emerged by day 2, peaked on day 4 (37.2 and 15.0&#xa0;µg/mL), and declined with immune reconstitution; rhizoferrin was also detected in bronchoalveolar lavage from a patient with mucormycosis. Analytically, the workflow links radiotracer uptake, high-mass-accuracy spatial ion mapping of peptides with lipids, and matrix-matched urinary LC-MS quantitation within the same infection model. This integrated platform enables spatially resolved mechanistic readouts and supports non-invasive metallophore-based diagnostics of invasive mucormycosis.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Infection metallomics of pulmonary mucormycosis: multi-omics study of siderophore secretion, neutrophil recruitment, and lipid remodeling in rat lungs

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月20日

查看全文
  • Dominika Luptáková,
  • Tereza Hřivnová Juříková,
  • Miloš Petřík,
  • Kateřina Dvořáková Bendová,
  • Barbora Neužilová,
  • Helena Marešová,
  • Andrea Palyzová,
  • Oldřich Benada,
  • Michaela Lackner,
  • Petr Hubáček,
  • Vladimír Havlíček

摘要

Invasive pulmonary mucormycosis caused by Rhizopus microsporus is often fatal, yet analytical tools to monitor fungal burden and host responses in vivo remain limited. We developed a multimodal infection metallomics workflow combining ⁶⁸Ga-desferrioxamine B PET/CT, high-resolution MALDI mass spectrometry imaging (MALDI-MSI), and targeted LC-MS to map fungal siderophore production and host tissue remodeling in a neutropenic rat model and in human samples. ⁶⁸Ga-desferrioxamine B was rapidly taken up by R. microsporus in vitro and accumulated in infected lungs in vivo. MALDI-MSI visualized rhizoferrin (m/z 435.1259, [M−H]⁻) and homorhizoferrin (m/z 449.1420, [M−H]⁻) confined to hyphal foci and absent from control lungs, whereas heme b was depleted and spatially segregated. Neutrophil α-defensins (RatNP-2/3/4) increased 14–60-fold and formed halos around lesions, showing an inverse trend with siderophore abundance. Lipid MSI revealed remodeling of anionic surfactant lipids, with depletion of short-chain phosphatidylglycerols and phosphatidic acid–derived species and accumulation of long-chain polyunsaturated phosphatidylglycerols and phosphatidylinositols in infected regions. Targeted LC-MS of serial urine showed that rhizoferrin and homorhizoferrin emerged by day 2, peaked on day 4 (37.2 and 15.0 µg/mL), and declined with immune reconstitution; rhizoferrin was also detected in bronchoalveolar lavage from a patient with mucormycosis. Analytically, the workflow links radiotracer uptake, high-mass-accuracy spatial ion mapping of peptides with lipids, and matrix-matched urinary LC-MS quantitation within the same infection model. This integrated platform enables spatially resolved mechanistic readouts and supports non-invasive metallophore-based diagnostics of invasive mucormycosis.

Graphical abstract