• Poster
  • P52

Toxoplasma gondii infection-driven genome instability is haplotype- and cell type-independent


Talk time:
Discussion time:
Location / Stream:
Poster- & Industrial Exhibition (LG)


Toxoplasma gondii infection-driven genome instability is haplotype- and cell type-independent


  • Parasite-Host Interaction
  • Veterinary Parasitology


Lisbeth Rojas Barón (Gießen / DE), Dr. Iván Conejeros (Gießen / DE), Simon Butterworth (London / GB), Dr. Moritz Treeck (London / GB), Prof. Dr. Carlos Hermosilla (Gießen / DE), Prof. Dr. Anja Taubert (Gießen / DE), Dr. Zahady Velásquez (Gießen / DE)


Abstract text

Introduction: Toxoplasma gondii is an obligate intracellular coccidian parasite, which is well known for its extraordinary capacity to modulate its host cell. The three main T. gondii clonal lineages exhibit different degrees of virulence. Thus, type 1 strains lead to widespread parasite dissemination and death in mice, whilst type 3 is considered avirulent. As recently demonstrated, T. gondii infections affect host cell cycle progression, chromosome segregation and cytokinesis, all hallmarks of genome instability triggered by genomic DNA damage.

Objective: We here studied whether T. gondii-driven genome instability is a parasite strain (haplotype)- or cell type-dependent event.

Materials & Methods: We here compared infections with T. gondii RH, Me49 and NED strains representing, type 1, 2 and 3 haplotypes. FACS-based analyses on cell cycle progression were performed in different primary human and bovine cell types (e. g. HUVEC, HFF and BUVEC). Both, immunofluorescence assays detecting ᵞH2Ax-related DNA damage foci and comet assays were used to estimate DNA damage in T. gondii-infected cells and controls. Activation of the DNA damage repair pathway was studied by Western blot-based quantification of related key proteins. Since a main source of intracellular DNA damage is enhanced ROS, we also analyzed intracellular and extracellular ROS concentrations in T. gondii-infected BUVEC by DCF-DA and AmplexRed assays, respectively.

Results: In line with recent observations on the RH strain, all cell types used were found arrested in S-phase showing increased proportions of binucleated cells. These findings were strain-independent since they also were observed in T. gondii NED and Me49 infections. In addition, all three haplotypes induced DNA strand breaks within 24 h p. i. Moreover, RH strain was shown to activate the host cell homologous recombination repair pathway. In addition, exclusively the first step of the non-homologous end-joining pathway was activated in host cells after 24 h p. i. Overall, no changes in intra- or extracellular ROS were detected in any infection.

Conclusion: Our data suggest that T. gondii infection-driven alteration of host cell cycle progression and cytokinesis is independent of the host cell type, host species origin and parasite haplotype. In addition, both T. gondii-driven host cellular DNA strand breaks and activation of the homologous recombination pathway occurred independent of host cellular ROS production.

  • © Conventus Congressmanagement & Marketing GmbH