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Infection and Immunity, January 2002, p. 62-68, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.62-68.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Reduced Infectivity of a Leishmania donovani Biopterin Transporter Genetic Mutant and Its Use as an Attenuated Strain for Vaccination

Barbara Papadopoulou, Gaétan Roy, Marie Breton, Christoph Kündig,,{dagger} Carole Dumas, Isabelle Fillion, Ajay K. Singh,,{ddagger} Martin Olivier, and Marc Ouellette*

Centre de Recherche en Infectiologie du Centre de Recherche du CHUL and Division de Microbiologie, Faculté de Médecine, Université Laval, Québec, Canada

Received 19 June 2001/ Returned for modification 27 August 2001/ Accepted 16 October 2001

Pterins are essential for the growth of Leishmania species, and recent work has led to the isolation of the biopterin transporter BT1. In this study, we inactivated the Leishmania donovani biopterin transporter BT1 by gene disruption mediated by homologous recombination. No transport of biopterin was detected in this mutant. The L. donovani BT1 null mutant showed a much lesser capacity for inducing infection in mice than wild-type parasites and could elicit protective immunity in mice susceptible to infection against a L. donovani challenge. Splenocytes isolated from mice immunized with the BT1 null mutant parasites produced significant amounts of interferon gamma following stimulation with L. donovani promastigotes as measured by enzyme-linked immunosorbent assay and enzyme-linked immunospot assays. Overall, these results show that by genetically manipulating the pterin transport in L. donovani, it is possible to generate an attenuated organism that could be part of a vaccination strategy.

* Corresponding author. Mailing address: Centre de Recherche en Infectiologie, CHUQ, pavillon CHUL, 2705 boul. Laurier, Ste-Foy, Québec, Canada G1V 4G2. Phone: 418-654 2705. Fax: 418-654 2715. E-mail: Marc.Ouellette{at}crchul.ulaval.ca.

Editor: W. A. Petri, Jr.

{dagger} Present address: Microcide Pharmaceuticals, Mountain View, Calif.

{ddagger} Present address: Division of Infectious Diseases, UCSF, San Francisco, Calif.

Infection and Immunity, January 2002, p. 62-68, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.62-68.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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