Remote control of tumour-targeted Salmonella enterica serovar Typhimurium by the use of L-arabinose as inducer of bacterial gene expression in vivo.
We have used Salmonella enterica serovar Typhimurium (S. typhimurium) which are able to colonize tumours besides spleen and liver. Bacteria were equipped with constructs encoding green fluorescent protein or luciferase as reporters under control of the promoter PBAD that is inducible with L-arabinose. Reporter genes could be induced in culture but also when the bacteria resided within the mouse macrophages J774A.1. More important, strong expression of reporters by the bacteria could be detected in mice after administration of L-arabinose. This was especially pronounced in bacteria colonizing tumours. Histology demonstrated that the bacteria had accumulated in and close to necrotic areas of tumours. Bacterial gene induction was observed in both regions. PBAD is tightly controlled also in vivo because gene E of bacteriophage PhiX174 could be introduced as inducible suicide gene. The possibility to deliberately induce genes in bacterial carriers within the host should render them extremely powerful tools for tumour therapy.
Loessner
Holger
H
Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. holger.loessner@helmholtz-hzi.de
Endmann
Anne
A
Leschner
Sara
S
Westphal
Kathrin
K
Rohde
Manfred
M
Miloud
Tewfik
T
Hämmerling
Günter
G
Neuhaus
Klaus
K
Weiss
Siegfried
S
D000818:Animals; D001089:Arabinose / Q000008:administration & dosage / Q000378:metabolism*; D001433:Bacteriolysis; D045744:Cell Line, Tumor; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000382:microbiology* / Q000628:therapy*; D011401:Promoter Regions, Genetic; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D001089:Arabinose