Proteomic Comparison between Hyphae and Spores Reveals Pathogenicity of Mucor Irregularis

Mucor irregularis, an emerging causative agent of disfiguring mucormycosis, demonstrates distinct clinical manifestations between hyphae and spore forms, though the pathogenic determinants between these two forms remain elusive. Utilizing TMT (tandem mass tag)-based quantitative proteomics (ProteomeXchange: PXD055430), we conducted a comparative analysis of these morphotypes, followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein–protein interaction network construction. Critically, we identified the following: (i) tRNA sulfur modification (NCS6) in spore dormancy maintenance; (ii) adenylate kinase (adenylate kinase 1)-mediated energy metabolism during germination; and (iii) COQ3-dependent mitochondrial function in spore germination. This first proteomic profiling of M. irregularis morphotypes delineates distinct phase-specific adaptations. Notably, the ribosomal and dormancy-associated machinery as NCS6 in spores contrasts sharply with the metabolic activation and upregulated virulence determinants as PAC1 in hyphae. Findings highlight NAT10 critical for spore readiness and RhoGEF GTPases central to hyphal invasion as particularly promising candidate therapeutic targets. Building upon this foundation, future investigations must now delineate the immunomodulatory roles of these effector proteins during host invasion to advance mucormycosis management strategies.