Lactococcus lactis
 Expressing either
 Staphylococcus aureus
 Fibronectin-Binding Protein A or
 Listeria monocytogenes
 Internalin A Can Efficiently Internalize and Deliver DNA in Human Epithelial Cells

Innocentin, Silvia; Guimarães, Valeria; Miyoshi, Anderson; Azevedo, Vasco; Langella, Philippe; Châtel, Jean-Marc; Lefèvre, François

doi:10.1128/aem.00825-09

Cited by 92 publications

(100 citation statements)

References 30 publications

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“…At this point, we have determined that wild-type ll27 possesses an ability to internalize or be internalized within intestinal cells. in contrast, innocentin et al (24) have reported that lactococci were noninvasive. On the basis of our own findings that L. lactis ll27 possesses an internalization property, we suggest the possibility that this organism might be exploited as a DnA vaccine delivery vehicle as well.…”

Section: Resultsmentioning

confidence: 90%

Probiotic and Antioxidative Properties ofL. LactisLL27 Isolated from Milk

Özdoğan

Akçelik

Aslım

et al. 2012

Biotechnology & Biotechnological Equipment

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Section: Resultsmentioning

confidence: 90%

Probiotic and Antioxidative Properties ofL. LactisLL27 Isolated from Milk

Özdoğan

Akçelik

Aslım

et al. 2012

Biotechnology & Biotechnological Equipment

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“…Previous studies quantified the BLG eukaryotic expression plasmid delivery by L. lactis using BLG protein-specific enzyme-linked immunosorbent assay (ELISA). 16,27) They suggested that plasmid DNA delivery by L. lactis in mice may be a stochastic event that is dependent on environmental factors, as some mice (30-50%) did not produce any BLG protein. 16) In contrast, our data indicated that DNA delivery in the small intestine by L. lactis occurred in all mice inoculated with L. lactis strains carrying a plasmid for NanoLuc expression, irrespective of mInlA expression.…”

Section: Discussionmentioning

confidence: 99%

Peyer’s Patches as a Portal for DNA Delivery by Lactococcus lactis in Vivo

Yano

Takahashi

Mori

et al. 2018

Biological & Pharmaceutical Bulletin

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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. Key words Lactococcus lactis;Peyer's patch; DNA delivery; Internalin A Vaccination with a plasmid containing the DNA sequence encoding an antigen has been of great interest of late as it can induce both humoral and cell-mediated immune responses. 1)Despite numerous studies, no DNA vaccines have been licensed for human use to date. The administration of naked DNA is less immunogenic in large animals and humans, probably due to the low level of protein expression.2) To improve the potency of DNA vaccination, various DNA delivery platforms, including electroporation, needle-free jet injection and liposomes, have been developed. 3,4) The use of bacteria as a delivery vehicle for DNA vaccines has emerged recently as a promising approach to enhance potency, 5) and one of the attractive features of the use of bacteria is the potential for oral administration to induce not only systemic but also mucosal immune responses. 5) Salmonella typhimurium and Listeria monocytogenes (L. monocytogenes) have been studied as experimental delivery vehicles as they are known to invade intestinal epithelial cells. 6) Even though the strains employed are extensively attenuated for virulence, the possibility of reversion to virulence as well as preexisting immunity limits their clinical use, especially for infants, the elderly and immunocompromised hosts. 7,8) The mechanisms involving DNA transfer from bacteria to mammalian cells and tissues remain to be clarified.The use of food-grade Lactococcus ...

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“…This fusion protein promoted the binding of L. lactis to porcine intestinal epithelial cells (Lindholm et al, 2004). Finally, expression in L. lactis of either a fibronectin binding protein from Staphylococcus aureus o r I n t e r n a l i n A f r o m Listeria monocytogenes promoted its binding to human epithelial cells and bacterial internalization, providing a tool for DNA delivery into eukaryotic cells (Innocentin et al, 2009). …”

Section: Engineered Lactic Acid Bacteria With Enhanced Adhesionmentioning

confidence: 99%