Development of a Stress-Inducible Controlled Expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces.

In recent years, recombinant lactic acid bacteria (LAB) have been successfully used as safe mucosal delivery vectors. Herein, we report on the development of a Stress-Inducible Controlled Expression (SICE) system in L. lactis for the production and delivery of proteins of health interest (both therapeutic and vaccine related) at mucosal surfaces.

Protection against human papillomavirus type 16-induced tumors in mice using non-genetically modified lactic acid bacteria displaying E7 antigen at its surface.

Human papillomavirus (HPV) is the causative agent of cervical cancer (CxCa) and the most commonly sexually transmitted pathogen worldwide. HPV type 16 (HPV-16) E7 oncoprotein is constitutively produced in CxCa and considered as a good antigen candidate for the development of new therapeutic CxCa vaccines. Here, we report the use of non-genetically modified, E7-expressing lactic acid bacteria (LAB) by using the cell-binding domain from Lactobacillus casei A2 phage lysin as a cell wall anchor.

LysA2, the Lactobacillus casei bacteriophage A2 lysin is an endopeptidase active on a wide spectrum of lactic acid bacteria.

The lysin gene (lysA2) of the Lactobacillus casei bacteriophage A2 was cloned and expressed in Escherichia coli. LysA2 is an endopeptidase that hydrolyzes the bond between the terminal D: -alanine of the peptidoglycan tetrapeptide and the aspartic acid residue that forms the bridge with the L: -lysine of a neighboring peptidoglycan chain, characteristic of Gram-positive bacteria included into the A4 peptidoglycan subgroup. This includes most lactobacilli, Lactococcus lactis, Pediococcus acidilactici, and Pediococcus pentosaceus, the walls of all of which were substrates for the enzyme.