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Role of the wbt Locus of Francisella tularensis in Lipopolysaccharide O-Antigen Biogenesis and Pathogenicity

Catherine Raynaud,^1,2, Karin L. Meibom,^1,2, Marie-Annick Lety,^1,2, Iharilalao Dubail,^1,2 Thomas Candela,³ Eric Frapy,^1,2 and Alain Charbit^1,2,*

Université Paris Descartes, Faculté de Médecine René Descartes, Paris F-75015, France,¹ Inserm, U570, Unité de Pathogénie des Infections Systémiques, Paris F-75015, France,² Unité Toxines et Pathogénie Bactérienne CNRS-URA2172, 28 rue de Dr Roux, 75724 Paris Cedex 15, France³

Received 5 September 2006/ Accepted 18 September 2006

Francisella tularensis is a highly infectious bacterial pathogen, responsible for the zoonotic disease tularemia. We screened a bank of transposon insertion mutants of F. tularensis subsp. holarctica LVS for colony morphology alterations and selected a mutant with a transposon insertion in wbtA, the first gene of the predicted lipopolysaccharide O-antigen gene cluster. Inactivation of wbtA led to the complete loss of O antigen, conferred serum sensitivity, impaired intracellular replication, and severely attenuated virulence in the mouse model. Notably, this mutant afforded protection against a challenge against virulent LVS.

Published ahead of print on 9 October 2006.

Editor: D. L. Burns

C.R., K.L.M., M.-A.L., and A.C. contributed equally to this work.

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