Novel applications of recombinant lactic acid bacteria in therapy and in metabolic engineering.

Lactic acid bacteria (LAB) are gaining importance due to their "generally recognized as safe" status, long-term use in food and beneficial, probiotic properties. They can acquire new, desirable traits by the incorporation of genes that allow the expression of heterologous proteins, and several patents and patent applications describe the use of recombinant LAB. We first focus on the available expression systems, their improvement towards "food-grade" status, and modes of regulating the expression. LAB have been used as vehicles for the delivery of proteins to the mucosal surfaces. Delivered proteins may interact with the immune system and have been shown to be effective, either as vaccines or as tolerance-inducing, anti-allergy agents in mice. Proteins with biological functions that could be used in therapy have also been delivered. Delivery of interleukin 10 (IL-10) in Crohn's disease, which was tested in a human phase I clinical trial and has proceeded to phase IIa, is the first example of use of recombinant LAB in humans. Another field of recombinant LAB application is metabolic engineering. Existing metabolic pathways have been modified to improve the properties of LAB as food fermentation starters, and heterologous metabolic enzymes have been introduced to LAB for the production of industrially relevant chemicals.