Lactococci are noninvasive bacteria frequently used as protein delivery vectors and, more recently, as in vitro and in vivo DNA delivery vehicles. We previously showed that a functional eukaryotic enhanced green fluorescent protein (eGFP) expression plasmid vector was delivered in epithelial cells by Lactococcus lactis producing Listeria monocytogenes internalin A (L. lactis InlA_), but this strategy is limited in vivo to transgenic mice and guinea pigs. In this study, we compare the internalization ability of L. lactis InlA_ and L. lactis producing either the fibronectin-binding protein A of Staphylococcus aureus (L. lactis FnBPA_) or its fibronectin binding domains C and D (L. lactis CD_). L. lactis FnBPA_ and L. lactis InlA_ showed comparable internalization rates in Caco-2 cells, while the internalization rate observed with L. lactis CD_ was lower. As visualized by conventional and confocal fluorescence microscopy, large clusters of L. lactis FnBPA_, L. lactis CD_, and L. lactis InlA_ were present in the cytoplasm of Caco-2 cells after internalization. Moreover, the internalization rates of Lactobacillus acidophilus NCFM and of an NCFM mutant strain with the gene coding for the fibronectin- binding protein (fbpA) inactivated were also evaluated in Caco-2 cells. Similar low internalization rates were observed for both wild-type L. acidophilus NCFM and the fbpA mutant, suggesting that commensal fibronectin binding proteins have a role in adhesion but not in invasion. L. lactis FnBPA_, L. lactis CD_, and L. lactis InlA_ were then used to deliver a eukaryotic eGFP expression plasmid in Caco-2 cells: flow cytometry analysis showed that the highest percentage of green fluorescent Caco-2 cells was observed after coculture with either L. lactis FnBPA_ or L. lactis InlA_. Analysis of the in vivo efficiency of these invasive recombinant strains is currently in progress to validate their potential as DNA vaccine delivery vehicles.