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

Ojeda SS, Wang ZJ, Mares CA, Chang TA, Li Q, Morris EG, Jerabek PA, Teale JM - BMC Microbiol. (2008)

Bottom Line: By 20 hours, there was significant tropism to the lung compared with other tissues.MicroPET images correlated with the biodistribution of isotope and bacterial burdens in analyzed tissues.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. ojeda@uthscsa.edu

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.

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Biodistribution of viable vs. non viable 35S labeled bacteria. As a mode to compare the localization of labeled bacteria, metabolic labeling was performed for F. tularensis subsp. novicida. The data represent an average of 3 mice per treatment and are expressed as cpm/g. Viable (unfixed) labeled F. tularensis subsp. novicida is found mainly in the lungs while there was an increase in non-viable (fixed) organisms localizing primarily to the gall bladder.
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Figure 3: Biodistribution of viable vs. non viable 35S labeled bacteria. As a mode to compare the localization of labeled bacteria, metabolic labeling was performed for F. tularensis subsp. novicida. The data represent an average of 3 mice per treatment and are expressed as cpm/g. Viable (unfixed) labeled F. tularensis subsp. novicida is found mainly in the lungs while there was an increase in non-viable (fixed) organisms localizing primarily to the gall bladder.

Mentions: To determine the effect of viability on bacterial trafficking, F. tularensis subsp. novicida metabolically labeled with 35S-L-methionine and 35S-L-cysteine was taken to a titer of 2 × 109 and then fixed in 4% paraformaldehyde. Subsequently labeled bacteria were administered to mice i.n, and the accumulation of label in various tissues was compared with that of non-fixed, viable organisms. The data are expressed as counts per minute/g (cpm/g) (Fig. 3) and indicate that the bulk of the label was present in the lungs at 20 hrs p.i when viable (unfixed) organisms were used but more evenly distributed among the tissues analyzed when non-viable (fixed) organisms were used. In addition, use of non-viable organisms resulted in a significant increase in label in the gall bladder compared with viable organisms.


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

Ojeda SS, Wang ZJ, Mares CA, Chang TA, Li Q, Morris EG, Jerabek PA, Teale JM - BMC Microbiol. (2008)

Biodistribution of viable vs. non viable 35S labeled bacteria. As a mode to compare the localization of labeled bacteria, metabolic labeling was performed for F. tularensis subsp. novicida. The data represent an average of 3 mice per treatment and are expressed as cpm/g. Viable (unfixed) labeled F. tularensis subsp. novicida is found mainly in the lungs while there was an increase in non-viable (fixed) organisms localizing primarily to the gall bladder.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651876&req=5

Figure 3: Biodistribution of viable vs. non viable 35S labeled bacteria. As a mode to compare the localization of labeled bacteria, metabolic labeling was performed for F. tularensis subsp. novicida. The data represent an average of 3 mice per treatment and are expressed as cpm/g. Viable (unfixed) labeled F. tularensis subsp. novicida is found mainly in the lungs while there was an increase in non-viable (fixed) organisms localizing primarily to the gall bladder.
Mentions: To determine the effect of viability on bacterial trafficking, F. tularensis subsp. novicida metabolically labeled with 35S-L-methionine and 35S-L-cysteine was taken to a titer of 2 × 109 and then fixed in 4% paraformaldehyde. Subsequently labeled bacteria were administered to mice i.n, and the accumulation of label in various tissues was compared with that of non-fixed, viable organisms. The data are expressed as counts per minute/g (cpm/g) (Fig. 3) and indicate that the bulk of the label was present in the lungs at 20 hrs p.i when viable (unfixed) organisms were used but more evenly distributed among the tissues analyzed when non-viable (fixed) organisms were used. In addition, use of non-viable organisms resulted in a significant increase in label in the gall bladder compared with viable organisms.

Bottom Line: By 20 hours, there was significant tropism to the lung compared with other tissues.MicroPET images correlated with the biodistribution of isotope and bacterial burdens in analyzed tissues.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. ojeda@uthscsa.edu

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.

Show MeSH
Related in: MedlinePlus