Revealing the dynamics of fungal disease with proteomics

Molecular Omics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The occurrence and distribution of new re-emerging fungal pathogens, along with rates antifungal resistance, are rising across the globe, correspondingly, so our awareness call for action to address this public health concern. To effectively detect, monitor, treat infections, biological insights into mechanisms that regulate pathogenesis, influence survival, promote resistance urgently needed. Mass spectrometry-based proteomics is a high-resolution technique enables identification quantification proteins diverse systems better understand biology driving phenotypes. In review, we highlight dynamic innovative applications characterize three critical pathogens (i.e., Candida spp., Cryptococcus Aspergillus spp.) causing disease in humans. We present strategies investigate host-pathogen interface, virulence factor production, protein-level drivers resistance. Through these studies, opportunities biomarker development, drug target discovery, immune system remodeling discussed, supporting use combat plethora diseases threatening global health.

Language: Английский

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Aspergillus fumigatus secondary metabolite pyripyropene is important for the dual biofilm formation with Pseudomonas aeruginosa

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

ABSTRACT The human pathogenic fungus Aspergillus fumigatus establishes dual biofilm interactions in the lungs with bacterium Pseudomonas aeruginosa . Screening of 21 A null mutants revealed seven (two G protein-coupled receptors, three mitogen-activated protein kinase a Gα protein, and one histidine receptor) reduced formation, specifically presence P. Transcriptional profiling metabolomics analysis secondary metabolites produced by these mutants, Δ gpaB ( encodes protein), showed GpaB controls production several important for interaction, including pyripyropene A, potent inhibitor mammalian acyl-CoA cholesterol acyltransferase. Deletion pyr2 , encoding non-reducing polyketide synthase essential biosynthesis, A. pyr2-P. growth, altered macrophage responses, attenuated mouse virulence chemotherapeutic murine model. We identified as novel player ecology this fungal pathogen. IMPORTANCE are two pathogens. Both organisms establish patients affected chronic lung pulmonary infections, such cystic fibrosis (CF) obstructive disease. Colonization is associated an increased risk colonization CF patients, disease prognosis poor when both pathogens present. Here, we genetic determinants establishment vitro fumigatus-P. interactions. Among them, interaction controlling metabolite pyripyropene. demonstrate that lack decreases between species well model aspergillosis. These results reveal complete role

Language: Английский

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Unveiling the fungal frontier: mycological insights into inflammatory bowel disease

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal that seriously affects the quality of life patients around world. It characterized by abdominal pain, diarrhea, and mucous bloody stools. There an urgent need for more accurate diagnosis effective treatment IBD. Accumulated evidence suggests gut microbiota plays important role in occurrence development inflammation. However, most studies on IBD have focused bacteria, while fungal microorganisms been neglected. Fungal dysbiosis can activate host protective immune pathway related to integrity epithelial barrier release variety pro-inflammatory cytokines trigger inflammatory response. Dectin-1, CARD9, IL-17 signaling pathways may be drivers dysbacteriosis In addition, fungal-bacterial interactions fungal-derived metabolites also play role. Based this information, we explored new strategies targeting intestinal group its metabolites, such as probiotics, antifungal drugs, diet therapy, fecal transplantation (FMT). This review aims summarize pathogenesis IBD, provide insights directions further research emerging field.

Language: Английский

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Theoretical conformational analysis of cross-linking bonds in fungal hydrophobin from Aspergillus fumigatus

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: April 23, 2025

Aspergillus fumigatus is a common saprophytic filamentous fungus that plays crucial role in nutrient cycling but can become an opportunistic pathogen, posing significant threat to immunocompromised individuals by causing invasive aspergillosis. A key feature of A. the presence hydrophobins-small amphipathic proteins form protective rodlet layer on conidial surfaces, facilitating biofilm formation and immune evasion. This structure, stabilized cross-linking disulfide bonds, provides resistance desiccation, oxidative stress, defenses, making these cross-links compelling target for study. In this work, we employ all-atom simulations, incorporating quantum mechanics/molecular mechanics (QM/MM) calculations, evaluate energy conformational effects bonds (CL1, CL2, CL3, CL4) assembly. By integrating QM/MM approaches, achieve detailed representation electronic structural properties within complex layer, gaining deeper insights into their essential maintaining stability integrity RodA hydrophobin protein from surface. We identify group ten residues influence directly cross-linking, with Gln23 Lys17 emerging as candidates experimental mutation control Our findings shed light molecular mechanisms underlying highlight potential targets disrupting offering promising avenues antifungal strategies.

Language: Английский

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