The macrophage-derived protein PTMA induces filamentation of the human fungal pathogen Candida albicans

Abstract

SUMMARY Evasion of killing by immune cells is crucial for fungal survival in the host. For the human fungal pathogen Candida albicans , internalization by macrophages induces a transition from yeast to filaments that promotes macrophage death and fungal escape. Nutrient deprivation, alkaline pH, and oxidative stress have been implicated as triggers of intraphagosomal filamentation; however, the impact of other host-derived factors remained unknown. Here, we show that lysates prepared from macrophage-like cell lines and primary macrophages robustly induce C. albicans filamentation. Enzymatic treatment of lysate implicates a phosphorylated protein, and bioactivity-guided fractionation coupled to mass spectrometry identifies the immunomodulatory phosphoprotein PTMA as a candidate trigger of C. albicans filamentation. Immunoneutralization of PTMA within lysate abolishes its activity, strongly supporting PTMA as a filament-inducing component of macrophage lysate. Adding to the known repertoire of physical factors, this work implicates a host protein in the induction of C. albicans filamentation within immune cells.

Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis

“…Filamentation inside the macrophages is coupled to cell wall remodelling, where β-1, 3-glucan masking is another important factor that plays a major role in determining the immune response of the host [ 19 ]. We determine the β -1, 3-glucan unmasking of control, CDTA treated and Δalr1 using dectin-1 Fc labelling that enables detection of exposed β-1,3-glucan in C .…”

Inference of cell type-specific gene regulatory networks on cell lineages from single cell omic datasets

“…HNRNPK has a number of regulatory functions across diverse cell types including as a regulator of hematopoiesis 60 . PTMA , which stands for prothymosin alpha is not well understood for its function but is implicated in growth and survival of cells of hematopoietic origin, and required for the filament-inducing activity of macrophage lysate 61 , which would be consistent with its expression in the hematopoietic lineage 62 . E17 had edges common to the Myeloid lineage spanning HSC-MPPs, MEMPs, Mast-cells, Megakaryocytes and Erythroid populations and had ENO1, NPM1, SNRPD1 in addition to HNRNPK and PTMA as top regulators (Fig.…”

“Under Pressure” – How fungi evade, exploit, and modulate cells of the innate immune system

“…A recent study, for instance, revealed that C. albicans senses the content of extracellular vesicles, which are released by immune cells, promoting filamentous growth [269] . Similarly, C. albicans has been shown to filament in response to the macrophage-derived protein PTMA [270] . Filamentation potentially prepares the fungus for future macrophage contacts since phagocytosis of hyphae is not only slower than internalization of yeast cells, but may lead to the formation of less microbicidal frustrated phagosomes [12] , [126] , [127] .…”