Research article

Rapid dissemination of Francisella tularensis and the effect of route of infection

Sandra S Ojeda^{* 1} , Zheng J Wang^{* 2} , Chris A Mares¹ , Tingtung A Chang³ , Qun Li⁵ , Elizabeth G Morris⁵ , Paul A Jerabek⁴ and Judy M Teale^1,5

¹Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX, 78229, USA

²MPI Research, 54943 North Main Street, Mattawan, MI, 49071, USA

³Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX, 78229, USA

⁴Research Imaging Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX, 78229, USA

⁵Department of Biology, University of Texas at San Antonio, One UTSA Circle San Antonio, TX, 78249, USA

author email corresponding author email* Contributed equally

BMC Microbiology 2008, 8:215doi:10.1186/1471-2180-8-215

Published:	9 December 2008

Abstract

Background

Francisella tularensis subsp. tularensis is classified as a Category A bioweapon that is capable of establishing a lethal infection in humans upon inhalation of very few organisms. However, the virulence mechanisms of this organism are not well characterized. Francisella tularensis subsp. novicida, which is an equally virulent subspecies in mice, was used in concert with a microPET scanner to better understand its temporal dissemination in vivo upon intranasal infection and how such dissemination compares with other routes of infection. Adult mice were inoculated intranasally with F. tularensis subsp. novicida radiolabeled with ⁶⁴Cu and imaged by microPET at 0.25, 2 and 20 hours post-infection.

Results

⁶⁴Cu labeled F. tularensis subsp. novicida administered intranasally or intratracheally were visualized in the respiratory tract and stomach at 0.25 hours post infection. By 20 hours, there was significant tropism to the lung compared with other tissues. In contrast, the images of radiolabeled F. tularensis subsp. novicida when administered intragastrically, intradermally, intraperitoneally and intravenouslly were more generally limited to the gastrointestinal system, site of inoculation, liver and spleen respectively. MicroPET images correlated with the biodistribution of isotope and bacterial burdens in analyzed tissues.

Conclusion

Our findings suggest that Francisella has a differential tissue tropism depending on the route of entry and that the virulence of Francisella by the pulmonary route is associated with a rapid bacteremia and an early preferential tropism to the lung. In addition, the use of the microPET device allowed us to identify the cecum as a novel site of colonization of Francisella tularensis subsp. novicida in mice.