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Infection and Immunity, August 2009, p. 3424-3431, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00196-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Reintroduction of Two Deleted Virulence Loci Restores Full Virulence to the Live Vaccine Strain of Francisella tularensis{triangledown}

Emelie Salomonsson,1,2 Kerstin Kuoppa,1 Anna-Lena Forslund,1 Carl Zingmark,3 Igor Golovliov,3 Anders Sjöstedt,3 Laila Noppa,1 and Åke Forsberg1,2*

FOI Swedish Defence Research Agency, Division of CBRN Defence and Security, 901 82 Umeå, Sweden,1 Umeå Centre for Microbial Research (UCMR) and Laboratory for Molecular Infection Medicine, Sweden (MIMS), Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden,2 Umeå Centre for Microbial Research (UCMR) and Laboratory for Molecular Infection Medicine (MIMS), Sweden, Department of Clinical Microbiology, Umeå University, 901 85 Umeå, Sweden3

Received 19 February 2009/ Returned for modification 30 March 2009/ Accepted 29 May 2009

A disadvantage of several old vaccines is that the genetic events resulting in the attenuation are often largely unknown and reversion to virulence cannot be excluded. In the 1950s, a live vaccine strain, LVS, was developed from a type B strain of Francisella tularensis, the causative agent of tularemia. LVS, which is highly attenuated for humans but still virulent for mice by some infection routes, has been extensively studied and found to protect staff from laboratory-acquired tularemia. The efforts to improve biopreparedness have identified a demand for a vaccine against tularemia. Recently the rapid progress in genomics of different Francisella strains has led to identification of several regions of differences (RDs). Two genes carried within RDs, pilA, encoding a putative type IV pilin, and FTT0918, encoding an outer membrane protein, have been linked to virulence. Interestingly, LVS has lost these two genes via direct repeat-mediated deletions. Here we show that reintroduction of the two deleted regions restores virulence of LVS in a mouse infection model to a level indistinguishable from that of virulent type B strains. The identification of the two attenuating deletion events could facilitate the licensing of LVS for use in humans.

* Corresponding author. Mailing address: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden. Phone: 46-90-106660. Fax: 46-90-106800. E-mail: ake.forsberg{at}molbiol.umu.se

{triangledown} Published ahead of print on 8 June 2009.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2009, p. 3424-3431, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00196-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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