A Bioluminescent Francisella tularensis SCHU S4 Strain Enables Noninvasive Tracking of Bacterial Dissemination and the Evaluation of Antibiotics in an Inhalational Mouse Model of Tularemia.
Bioluminescence imaging (BLI) enables real-time, noninvasive tracking of infection in vivo and longitudinal infection studies. In this study, a bioluminescent Francisella tularensis strain, SCHU S4-lux, was used to develop an inhalational infection model in BALB/c mice. Mice were infected intranasally, and the progression of infection was monitored in real time using BLI. A bioluminescent signal was detectable from 3 days postinfection (3 dpi), initially in the spleen and then in the liver and lymph nodes, before finally becoming systemic. The level of bioluminescent signal correlated with bacterial numbers in vivo, enabling noninvasive quantification of bacterial burdens in tissues. Treatment with levofloxacin (commencing at 4 dpi) significantly reduced the BLI signal. Furthermore, BLI was able to distinguish noninvasively between different levofloxacin treatment regimens and to identify sites of relapse following treatment cessation. These data demonstrate that BLI and SCHU S4-lux are suitable for the study of F. tularensis pathogenesis and the evaluation of therapeutics for tularemia.
Bacterial Pathogenesis Research Group, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom c.hall5@herts.ac.uk.
Charlotte A
CA
Hall
CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
Helen C
HC
Flick-Smith
CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
Sarah V
SV
Harding
Bacterial Pathogenesis Research Group, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.|CBR Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom.
Helen S
HS
Atkins
Bacterial Pathogenesis Research Group, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
Richard W
RW
Titball
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005604:Francisella tularensis / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D064704:Levofloxacin / Q000494:pharmacology; D008099:Liver / Q000382:microbiology; D008163:Luminescent Measurements; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000382:microbiology; D014406:Tularemia / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology*
D000900:Anti-Bacterial Agents; D064704:Levofloxacin
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