Improving health from the inside: Use of engineered intestinal microorganisms as in situ cytokine delivery system.

Abstract:

:The anti-inflammatory cytokine interleukin-10 and its viral homologs were chosen as model proteins for the development of drug delivery systems based on probiotic carriers like E. coli Nissle 1917, E. coli G3/10, and Saccharomyces boulardii. Exterior cytokine secretion was achieved by a modified E. coli hemolysin transporter. Release of interleukin-10 transported to the periplasm via the OmpF signal peptide was enabled by a T4 phage lysis system under control of the araC PBAD activator-promoter. The yield of interleukin-10 delivered by the phage lysis system was too low for functional analysis whereas the fusion protein secreted by the hemolysin transporter proved to be biologically inactive. Moreover, partial processing of the fusion protein by the E. coli membrane protease OmpT had no effect on the protein's functionality. Using the α-mating factor signal sequence, the yeast S. boulardii proved to be suitable for secretory expression of biologically active viral interleukin-10.

journal_name

Bioengineered

journal_title

Bioengineered

authors

Pöhlmann C,Thomas M,Förster S,Brandt M,Hartmann M,Bleich A,Gunzer F

doi

10.4161/bioe.22646

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

172-9

issue

3

eissn

2165-5979

issn

2165-5987

pii

22646

journal_volume

4

pub_type

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