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2016 ; 11
(5
): e0155338
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Composing a Tumor Specific Bacterial Promoter
#MMPMID27171245
Deyneko IV
; Kasnitz N
; Leschner S
; Weiss S
PLoS One
2016[]; 11
(5
): e0155338
PMID27171245
show ga
Systemically applied Salmonella enterica spp. have been shown to invade and
colonize neoplastic tissues where it retards the growth of many tumors. This
offers the possibility to use the bacteria as a vehicle for the tumor specific
delivery of therapeutic molecules. Specificity of such delivery is solely
depending on promoter sequences that control the production of a target molecule.
We have established the functional structure of bacterial promoters that are
transcriptionally active exclusively in tumor tissues after systemic application.
We observed that the specific transcriptional activation is accomplished by a
combination of a weak basal promoter and a strong FNR binding site. This
represents a minimal set of control elements required for such activation. In
natural promoters, additional DNA remodeling elements are found that alter the
level of transcription quantitatively. Inefficiency of the basal promoter ensures
the absence of transcription outside tumors. As a proof of concept, we compiled
an artificial promoter sequence from individual motifs representing FNR and basal
promoter and showed specific activation in a tumor microenvironment. Our results
open possibilities for the generation of promoters with an adjusted level of
expression of target proteins in particular for applications in bacterial tumor
therapy.
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