Beckie Tempel

Medical Microbiology & Immunology

Rebecca Tempel, Xin-He Lai, Lidia Crosa, Briana Kozlowicz, Fred Heffron

Attenuated Francisella  Mutants Protect Mice Against Wild-Type Challenge

Abstract: Francisella tularensis is the bacterial pathogen that causes

tularemia, a debilitating and potentially fatal disease that affects

humans and a broad range of animals. Infections can be acquired

through multiple routes, which include bites from an arthropod vector

such as a tick or deerfly, skin lesions, ingestion of contaminated

food or water, and, most dangerously, by inhalation of as few as 10

bacteria.  In addition to the thousands of naturally occurring cases

reported each year, F. tularensis has been developed for use

as an effective biological weapon. Despite these factors, there is

currently no approved vaccine available in the United States or

Europe.

Our research is focused on designing a rationally

attenuated live vaccine strain of F. tularensis. To this end,

we generated a library of Francisella transposon mutants and

screened them for attenuation in macrophages and avirulence in mice.

The mutant strains that exhibited attenuation in mice were further

tested to determine if they could provide protection against

subsequent infection with wild-type bacteria. These studies led to the

identification of four F. tularensis genes that exhibit

appreciable potential as the basis for a live vaccine in that the

mutant derivatives protect mice against challenge with high doses of

the parental F. tularensis strain.