A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity

Mark D. Lavine, Laura J. Knoll, Peggy J. Rooney, Gustavo Arrizabalaga

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Toxoplasma gondii is an important opportunistic pathogen in immunocompromised individuals. Successful propagation in an infected host by this obligate intracellular parasite depends on its ability to enter and exit host cells. Egress from the cell can be artificially induced by causing fluxes of calcium within the parasite with the use of calcium ionophores. While this ionophore-induced egress (IIE) has been characterized in detail, it is not known whether it mimics a normal physiological process of the parasite. This is underscored by the fact that mutants in IIE do not exhibit strong defects in any of the normal growth characteristics of the parasite in tissue culture. We have isolated and characterized a T. gondii mutant that along with a delay in IIE exhibits a severe defect in establishing a successful infection in vivo. In tissue culture this mutant displays normal ability to invade, divide within cells and convert into the latent encysted bradyzoite form. Nevertheless, mice infected with this mutant are less likely to die and carry less brain cysts than those infected with wild type parasites. Thus, our results suggest that normal response to calcium fluxes plays an important role during in vivo development of T. gondii.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalMolecular and Biochemical Parasitology
Volume155
Issue number2
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

Toxoplasma
Virulence
Parasites
Calcium
Ionophores
Physiological Phenomena
Calcium Ionophores
Cysts
Brain
Growth
Infection

Keywords

  • Bradyzoite
  • Calcium
  • Egress
  • Toxoplasma
  • Virulence

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

Cite this

A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity. / Lavine, Mark D.; Knoll, Laura J.; Rooney, Peggy J.; Arrizabalaga, Gustavo.

In: Molecular and Biochemical Parasitology, Vol. 155, No. 2, 10.2007, p. 113-122.

Research output: Contribution to journalArticle

@article{fe460bb9c710413f89deac71db687607,
title = "A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity",
abstract = "Toxoplasma gondii is an important opportunistic pathogen in immunocompromised individuals. Successful propagation in an infected host by this obligate intracellular parasite depends on its ability to enter and exit host cells. Egress from the cell can be artificially induced by causing fluxes of calcium within the parasite with the use of calcium ionophores. While this ionophore-induced egress (IIE) has been characterized in detail, it is not known whether it mimics a normal physiological process of the parasite. This is underscored by the fact that mutants in IIE do not exhibit strong defects in any of the normal growth characteristics of the parasite in tissue culture. We have isolated and characterized a T. gondii mutant that along with a delay in IIE exhibits a severe defect in establishing a successful infection in vivo. In tissue culture this mutant displays normal ability to invade, divide within cells and convert into the latent encysted bradyzoite form. Nevertheless, mice infected with this mutant are less likely to die and carry less brain cysts than those infected with wild type parasites. Thus, our results suggest that normal response to calcium fluxes plays an important role during in vivo development of T. gondii.",
keywords = "Bradyzoite, Calcium, Egress, Toxoplasma, Virulence",
author = "Lavine, {Mark D.} and Knoll, {Laura J.} and Rooney, {Peggy J.} and Gustavo Arrizabalaga",
year = "2007",
month = "10",
doi = "10.1016/j.molbiopara.2007.06.004",
language = "English (US)",
volume = "155",
pages = "113--122",
journal = "Molecular and Biochemical Parasitology",
issn = "0166-6851",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - A Toxoplasma gondii mutant defective in responding to calcium fluxes shows reduced in vivo pathogenicity

AU - Lavine, Mark D.

AU - Knoll, Laura J.

AU - Rooney, Peggy J.

AU - Arrizabalaga, Gustavo

PY - 2007/10

Y1 - 2007/10

N2 - Toxoplasma gondii is an important opportunistic pathogen in immunocompromised individuals. Successful propagation in an infected host by this obligate intracellular parasite depends on its ability to enter and exit host cells. Egress from the cell can be artificially induced by causing fluxes of calcium within the parasite with the use of calcium ionophores. While this ionophore-induced egress (IIE) has been characterized in detail, it is not known whether it mimics a normal physiological process of the parasite. This is underscored by the fact that mutants in IIE do not exhibit strong defects in any of the normal growth characteristics of the parasite in tissue culture. We have isolated and characterized a T. gondii mutant that along with a delay in IIE exhibits a severe defect in establishing a successful infection in vivo. In tissue culture this mutant displays normal ability to invade, divide within cells and convert into the latent encysted bradyzoite form. Nevertheless, mice infected with this mutant are less likely to die and carry less brain cysts than those infected with wild type parasites. Thus, our results suggest that normal response to calcium fluxes plays an important role during in vivo development of T. gondii.

AB - Toxoplasma gondii is an important opportunistic pathogen in immunocompromised individuals. Successful propagation in an infected host by this obligate intracellular parasite depends on its ability to enter and exit host cells. Egress from the cell can be artificially induced by causing fluxes of calcium within the parasite with the use of calcium ionophores. While this ionophore-induced egress (IIE) has been characterized in detail, it is not known whether it mimics a normal physiological process of the parasite. This is underscored by the fact that mutants in IIE do not exhibit strong defects in any of the normal growth characteristics of the parasite in tissue culture. We have isolated and characterized a T. gondii mutant that along with a delay in IIE exhibits a severe defect in establishing a successful infection in vivo. In tissue culture this mutant displays normal ability to invade, divide within cells and convert into the latent encysted bradyzoite form. Nevertheless, mice infected with this mutant are less likely to die and carry less brain cysts than those infected with wild type parasites. Thus, our results suggest that normal response to calcium fluxes plays an important role during in vivo development of T. gondii.

KW - Bradyzoite

KW - Calcium

KW - Egress

KW - Toxoplasma

KW - Virulence

UR - http://www.scopus.com/inward/record.url?scp=34547761359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547761359&partnerID=8YFLogxK

U2 - 10.1016/j.molbiopara.2007.06.004

DO - 10.1016/j.molbiopara.2007.06.004

M3 - Article

C2 - 17643508

AN - SCOPUS:34547761359

VL - 155

SP - 113

EP - 122

JO - Molecular and Biochemical Parasitology

JF - Molecular and Biochemical Parasitology

SN - 0166-6851

IS - 2

ER -