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


ABSTRACT: 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.

SUBMITTER: Case NT 

PROVIDER: S-EPMC8454912 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Case Nicola T NT   Duah Kwamaa K   Larsen Brett B   Wong Cassandra J CJ   Gingras Anne-Claude AC   O'Meara Teresa R TR   Robbins Nicole N   Veri Amanda O AO   Whitesell Luke L   Cowen Leah E LE  

Cell reports 20210801 8


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  ...[more]

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