Genomic insights into host and parasite interactions during intracellular infection by Toxoplasma gondii

• Published in: PloS one Vol. 17; no. 9; p. e0275226
• Main Authors: Ulahannan, Netha, Cutler, Ronald, Doña-Termine, Reanna, Simões-Pires, Claudia A, Wijetunga, N Ari, Croken, Matthew McKnight, Johnston, Andrew D, Kong, Yu, Maqbool, Shahina B, Suzuki, Masako, Greally, John M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-09-2022; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Annotations; Binding sites; Biology and Life Sciences; Cell activation; Cell division; Cell signaling; Chromatin; Chromatin - genetics; Diagnosis; DNA methylation; Extracellular matrix; Fibroblasts; Gene expression; Gene Expression Profiling; Gene mapping; Genes; Genetic aspects; Genetic transcription; Genomes; Genomics; Humans; Infections; Intracellular; Metabolism; Molecular interactions; Ontology; Parasites; Parasites - genetics; Parasitic diseases; Pathogens; Perturbation; Phase transitions; Regulation; Regulatory sequences; Research and Analysis Methods; Signaling; Tata box; Toxoplasma; Toxoplasma - genetics; Toxoplasma gondii; Toxoplasmosis - genetics; Toxoplasmosis - parasitology; Transcription activation; Transcription factors; Transcription Factors - genetics; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0275226

To gain insights into the molecular interactions of an intracellular pathogen and its host cell, we studied the gene expression and chromatin states of human fibroblasts infected with the Apicomplexan parasite Toxoplasma gondii. We show a striking activation of host cell genes that regulate a number of cellular processes, some of which are protective of the host cell, others likely to be advantageous to the pathogen. The simultaneous capture of host and parasite genomic information allowed us to gain insights into the regulation of the T. gondii genome. We show how chromatin accessibility and transcriptional profiling together permit novel annotation of the parasite's genome, including more accurate mapping of known genes and the identification of new genes and cis-regulatory elements. Motif analysis reveals not only the known T. gondii AP2 transcription factor-binding site but also a previously-undiscovered candidate TATA box-containing motif at one-quarter of promoters. By inferring the transcription factor and upstream cell signaling responses involved in the host cell, we can use genomic information to gain insights into T. gondii's perturbation of host cell physiology. Our resulting model builds on previously-described human host cell signalling responses to T. gondii infection, linked to induction of specific transcription factors, some of which appear to be solely protective of the host cell, others of which appear to be co-opted by the pathogen to enhance its own survival.