Disseminated infection with Talaromyces marneffei can involve several organs, yet most molecular studies still examine one tissue at a time. A new study in iMetaMed provides an organ-resolved view of how the host responds across the liver, lung and spleen in an immunosuppressed mouse model.
Researchers at Guangxi Medical University assessed fungal burden and tissue pathology seven days after infection using colony-forming unit assays and H&E and PAS staining. Liver, lung and spleen samples from infected and control mice then underwent LC-MS/MS-based global proteome, acetylome, lactylome, phosphoproteome and ubiquitinome profiling. These datasets capture thousands of proteins and tens of thousands of modification sites across the three organs.
Across organs, infection was associated with acute-phase proteins and immune pathways, together with marked changes in glucose, amino acid and lipid metabolism. But the shared response was only part of the picture. The liver, lung and spleen also had distinct protein-abundance and modification patterns, indicating that a disseminated pathogen encounters different host regulatory environments as it spreads.
The liver showed especially prominent ubiquitination-related changes that accompanied shifts in protein abundance, whereas the spleen had the broadest set of differential acetylation sites. Lactylation-associated signals and several histone modifications were most marked in the liver. Because the work used whole-organ homogenates, these patterns could reflect changes within cells, differences in cellular composition, or both.
At the level of individual lysine positions, overlap among ubiquitination, acetylation and lactylation was limited. Yet functional analysis repeatedly pointed to related pathways, particularly metabolic pathways and immune signaling. This pattern suggests that distinct modification systems may contribute to a common host response through different molecular sites, rather than through a single uniform switch.
The team also used the phosphoproteomic data to infer kinase-associated signatures computationally. The predicted patterns differed by organ, so the analysis was used to prioritize hypotheses rather than to claim directly measured kinase activity. Mapping these signatures to known drug-target relationships produced candidate compounds for exploratory testing; pitavastatin was also selected as a metabolism-informed candidate.
In the exploratory in vivo study, pitavastatin significantly reduced fungal burden in the liver. Changes in lung and spleen burden did not reach statistical significance, and pitavastatin-treated mice showed improved survival relative to vehicle controls. The experiment did not include a standard antifungal comparator, so the findings do not establish clinical benefit, a replacement for antifungal treatment, or the mechanism responsible for the observed effects.
By bringing protein abundance and four modification layers together across organs, the study provides a resource for investigating host-pathogen interactions in disseminated talaromycosis. The authors note that the analysis captures a single time point and that its kinase predictions need direct biochemical validation. Future work can use this map to test cell-type-specific mechanisms and clarify whether the highlighted pathways can support host-directed therapeutic strategies.
