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Infection and Immunity, May 2006, p. 2613-2618, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2613-2618.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Leishmania donovani Requires Functional Cdc42 and Rac1 To Prevent Phagosomal Maturation

M. Lerm,{dagger}* Å. Holm,{dagger} Å. Seiron, E. Särndahl, K.-E. Magnusson, and B. Rasmusson

Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden

Received 20 October 2005/ Returned for modification 28 November 2005/ Accepted 1 February 2006

Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C{alpha}. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation.

* Corresponding author. Mailing address: Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. Phone: 46 13 22 47 79. Fax: 46 13 22 47 89. E-mail: marle{at}imk.liu.se.

Editor: J. T. Barbieri

{dagger} M.L. and Å.H. contributed equally.

Infection and Immunity, May 2006, p. 2613-2618, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2613-2618.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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