Photonic detection of bacterial pathogens in living hosts.
The study of pathogenic processes is often limited to ex vivo assays and cell-culture correlates. A greater understanding of infectious diseases would be facilitated by in vivo analyses. Therefore, we have developed a method for detecting bacterial pathogens in a living host and used this method to evaluate disease processes for strains of Salmonella typhimurlum that differ in their virulence for mice. Three strains of Salmonella were marked with bioluminescence through transformation with a plasmid conferring constitutive expression of bacterial luciferase. Detection of photons transmitted through tissues of animals infected with bioluminescent Salmonella allowed localization of the bacteria to specific tissues. In this manner progressive infections were distinguished from those that were persistent or abortive. We observed patterns of bioluminescence that suggested the caecum may play a pivotal role in Salmonella pathogenesis. In vivo efficacy of an antibiotic was monitored using this optical method. This study demonstrates that real time non-invasive analyses of pathogenic events and pharmacological monitoring can be performed in vivo.
Contag
C H
CH
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305-5402, USA. ccontag@cmgm.stanford.edu
Contag
P R
PR
Mullins
J I
JI
Spilman
S D
SD
Stevenson
D K
DK
Benaron
D A
DA
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000493:pharmacokinetics; D018450:Disease Progression; D007420:Intestine, Large / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D008168:Lung / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010784:Photomicrography / Q000379:methods*; D010957:Plasmids; D012481:Salmonella Infections, Animal / Q000188:drug therapy / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity*; D013154:Spleen / Q000382:microbiology; D014169:Transformation, Bacterial; D014774:Virulence
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D008156:Luciferases