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Molecular and Cellular Biology, December 2000, p. 9399-9408, Vol. 20, No. 24
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Ionophore-Resistant Mutants of Toxoplasma gondii Reveal Host Cell Permeabilization as an Early Event in Egress

Michael W. Black,dagger Gustavo Arrizabalaga, and John C. Boothroyd*

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5124

Received 21 June 2000/Returned for modification 24 August 2000/Accepted 20 September 2000

Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. Invasion and egress by this protozoan parasite are rapid events that are dependent upon parasite motility and appear to be directed by fluctuations in intracellular [Ca2+]. Treatment of infected host cells with the calcium ionophore A23187 causes the parasites to undergo rapid egress in a process termed ionophore-induced egress (IIE). In contrast, when extracellular parasites are exposed to this ionophore, they quickly lose infectivity (termed ionophore-induced death [IID]). From among several Iie- mutants described here, two were identified that differ in several attributes, most notably in their resistance to IID. The association between the Iie- and Iid- phenotypes is supported by the observation that two-thirds of mutants selected as Iid- are also Iie-. Characterization of three distinct classes of IIE and IID mutants revealed that the Iie- phenotype is due to a defect in a parasite-dependent activity that normally causes infected host cells to be permeabilized just prior to egress. Iie- parasites underwent rapid egress when infected cells were artificially permeabilized by a mild saponin treatment, confirming that this step is deficient in the Iie- mutants. A model is proposed that includes host cell permeabilization as a critical part of the signaling pathway leading to parasite egress. The fact that Iie- mutants are also defective in early stages of the lytic cycle indicates some commonality between these normal processes and IIE.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Fairchild Building, Room D305, 300 Pasteur Dr., Stanford University School of Medicine, Stanford, CA 94305-5124. Phone: (650) 723-7984. Fax: (650) 723-6853. E-mail: john.boothroyd{at}stanford.edu.

dagger Present address: Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom.

Molecular and Cellular Biology, December 2000, p. 9399-9408, Vol. 20, No. 24
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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