RRC ID 56599
Author Yano A, Takahashi K, Mori Y, Watanabe S, Hanamura Y, Sugiyama T, Inoue N.
Title Peyer's Patches as a Portal for DNA Delivery by Lactococcus lactis in Vivo.
Journal Biol Pharm Bull
Abstract Application of food-grade Lactococcus lactis (L. lactis) as a safe delivery tool for DNA vaccines and therapeutic proteins has been well investigated. Although some studies showed that eukaryotic expression plasmids were transferred from L. lactis to enterocytes, the precise mechanism of the DNA transfer remains unknown. In this study, we generated an invasive L. lactis strain that expresses "murinized" Internalin A, an invasin of intracellular bacteria Listeria monocytogenes with two amino acid alterations for invasion into murine cells, and confirmed that this L. lactis strain delivered DNA in an invasin-dependent manner into a monolayer of epithelial cells polarized to mimic the gastrointestinal tract environment. Although invasive L. lactis inoculated orally can deliver DNA into enterocytes in the gastrointestinal tract of mice, the efficiency of DNA transfer was similar to that of non-invasive L. lactis strain, suggesting that the in vivo DNA transfer from L. lactis occurs invasin-independently. A ligated-intestinal loop assay, a method for a short-term culturing of the whole intestine filled with materials to evaluate the interaction of the materials with intestinal cells, demonstrated that both non-invasive and invasive L. lactis strains were present in the Peyer's patches of the small intestine. On the other hand, few L. lactis was detected in the non-Peyer's patch epithelial region. Thus, our observations lead us to speculate that DNA transfer from L. lactis occurs predominantly in the Peyer's patches in an invasin-independent manner.
Volume 41(2)
Pages 190-197
Published 2018-1-1
DOI 10.1248/bpb.b17-00657
PMID 29386479
MeSH Administration, Oral Animals Bacterial Proteins / administration & dosage Bacterial Proteins / chemistry Bacterial Proteins / genetics Bacterial Proteins / metabolism* Bacterial Translocation Biological Transport Caco-2 Cells Cell Line Cell Polarity DNA, Recombinant / administration & dosage DNA, Recombinant / metabolism* Drug Delivery Systems* Female Food Microbiology Humans Intestinal Mucosa / cytology Intestinal Mucosa / metabolism Intestinal Mucosa / microbiology Intestine, Small / cytology Intestine, Small / metabolism Intestine, Small / microbiology Lactococcus lactis / cytology Lactococcus lactis / genetics Lactococcus lactis / physiology* Listeria monocytogenes / cytology Listeria monocytogenes / genetics Listeria monocytogenes / physiology Mice Mice, Inbred C57BL Microorganisms, Genetically-Modified / cytology Microorganisms, Genetically-Modified / genetics Microorganisms, Genetically-Modified / physiology* Peyer's Patches / cytology Peyer's Patches / metabolism* Peyer's Patches / microbiology Recombinant Fusion Proteins / administration & dosage Recombinant Fusion Proteins / metabolism Vaccines, DNA / administration & dosage Vaccines, DNA / metabolism*
IF 1.54
Times Cited 4
Human and Animal Cells CACO-2(RCB0988)