Dataset Information

A positive feedback loop controls Toxoplasma chronic differentiation

ABSTRACT: Successful infection strategies must balance pathogen amplification and persistence. In Toxoplasma gondii, this is accomplished through differentiation into dedicated cyst-forming chronic stages that avoid clearance by the host immune system. The transcription factor BFD1 is both necessary and sufficient for stage conversion; however, its regulation is not understood. We examine five factors transcriptionally activated by BFD1. One of these is a cytosolic RNA-binding protein of the CCCH-type zinc finger family, which we name BFD2. Parasites lacking BFD2 fail to induce BFD1 and are consequently unable to fully differentiate in culture or in mice. BFD2 interacts with the BFD1 transcript under stress and deletion of BFD2 reduces BFD1 protein levels, but not mRNA abundance. The reciprocal effects on BFD2 transcription and BFD1 translation outline a positive feedback loop that enforces commitment to differentiation. BFD2 helps explain how parasites commit to the chronic gene-expression program and elucidates how the balance between proliferation and persistence is achieved over the course of infection.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Toxoplasma Gondii Me49

SUBMITTER: Alex Chan

LAB HEAD: Sebastian Lourido

PROVIDER: PXD039648 | Pride | 2023-08-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20221018_LouridoLab_AC_Fraction_1.raw	Raw
	20221018_LouridoLab_AC_Fraction_2.raw	Raw
	20221018_LouridoLab_AC_Fraction_3.raw	Raw
	20221018_LouridoLab_AC_Fraction_4.raw	Raw
	20221018_LouridoLab_AC_Fraction_5.raw	Raw

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Publications

A positive feedback loop controls Toxoplasma chronic differentiation.

Licon M Haley MH Giuliano Christopher J CJ Chan Alex W AW Chakladar Sundeep S Eberhard Julia N JN Shallberg Lindsey A LA Chandrasekaran Sambamurthy S Waldman Benjamin S BS Koshy Anita A AA Hunter Christopher A CA Lourido Sebastian S

Nature microbiology 20230420 5

Successful infection strategies must balance pathogen amplification and persistence. In the obligate intracellular parasite Toxoplasma gondii this is accomplished through differentiation into dedicated cyst-forming chronic stages that avoid clearance by the host immune system. The transcription factor BFD1 is both necessary and sufficient for stage conversion; however, its regulation is not understood. In this study we examine five factors that are transcriptionally activated by BFD1. One of the ...[more]

PMID: 37081202

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