A Toxoplasma gondii patatin-like phospholipase contributes to host cell invasion.

Autor: Wilson SK; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Linden Drive, Madison, Wisconsin, United States of America., Heckendorn J; INSERM, Université Montpellier, Montpellier, France., Martorelli Di Genova B; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Linden Drive, Madison, Wisconsin, United States of America., Koch LL; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Linden Drive, Madison, Wisconsin, United States of America., Rooney PJ; Stratatech Corporation, Charmany Drive, Madison, Wisconsin, United States of America., Morrissette N; Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, United States of America., Lebrun M; INSERM, Université Montpellier, Montpellier, France., Knoll LJ; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Linden Drive, Madison, Wisconsin, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Jul 06; Vol. 16 (7), pp. e1008650. Date of Electronic Publication: 2020 Jul 06 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1008650
Abstrakt: Toxoplasma gondii is an obligate intracellular parasite that can invade any nucleated cell of any warm-blooded animal. In a previous screen to identify virulence determinants, disruption of gene TgME49_305140 generated a T. gondii mutant that could not establish a chronic infection in mice. The protein product of TgME49_305140, here named TgPL3, is a 277 kDa protein with a patatin-like phospholipase (PLP) domain and a microtubule binding domain. Antibodies generated against TgPL3 show that it is localized to the apical cap. Using a rapid selection FACS-based CRISPR/Cas-9 method, a TgPL3 deletion strain (ΔTgPL3) was generated. ΔTgPL3 parasites have defects in host cell invasion, which may be caused by reduced rhoptry secretion. We generated complementation clones with either wild type TgPL3 or an active site mutation in the PLP domain by converting the catalytic serine to an alanine, ΔTgPL3::TgPL3S1409A (S1409A). Complementation of ΔTgPL3 with wild type TgPL3 restored all phenotypes, while S1409A did not, suggesting that phospholipase activity is necessary for these phenotypes. ΔTgPL3 and S1409A parasites are also virtually avirulent in vivo but induce a robust antibody response. Vaccination with ΔTgPL3 and S1409A parasites protected mice against subsequent challenge with a lethal dose of Type I T. gondii parasites, making ΔTgPL3 a compelling vaccine candidate. These results demonstrate that TgPL3 has a role in rhoptry secretion, host cell invasion and survival of T. gondii during acute mouse infection.
Competing Interests: PJR is currently employed by the Stratatech Corporation. Her affiliation with this company did not affect this study in any way. This affiliation does not alter our adherence to all PLOS Pathogens policies on sharing data and materials. The other authors have declared that no competing interests exist.
Databáze: MEDLINE
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