Novel Strategies for Efficient Production and Delivery of Live Biotherapeutics and Biotechnological Uses of Lactococcus lactis: The Lactic Acid Bacterium Model

Abstract

Lactic acid bacteria (LAB) are traditionally used in fermentation and food preservation processes and are recognized as safe for consumption. Recently, they have attracted attention due to their health-promoting properties; many species are already widely used as probiotics for treatment or prevention of various medical conditions, including inflammatory bowel diseases, infections, and autoimmune disorders. Some LAB, especially Lactococcus lactis , have been engineered as live vehicles for delivery of DNA vaccines and for production of therapeutic biomolecules. Here, we summarize work on engineering of LAB, with emphasis on the model LAB, L. lactis . We review the various expression systems for the production of heterologous proteins in Lactococcus spp. and its use as a live delivery system of DNA vaccines and for expression of biotherapeutics using the eukaryotic cell machinery. We have included examples of molecules produced by these expression platforms and their application in clinical disorders. We also present the CRISPR-Cas approach as a novel methodology for the development and optimization of food-grade expression of useful substances, and detail methods to improve DNA delivery by LAB to the gastrointestinal tract. Finally, we discuss perspectives for the development of medical applications of recombinant LABs involving animal model studies and human clinical trials, and we touch on the main safety issues that need to be taken into account so that bioengineered versions of these generally recognized as safe organisms will be considered acceptable for medical use.

Isolation and characterization ofLactococcus garvieaefrom rainbow trout, Onchorhyncus mykiss, from California, USA

“…Despite this, studies on L. garvieae biofilms are lacking. Their formation has been described in the closely related L. lactis (Diaz et al., 2016; Kives et al., 2005; Oxaran et al., 2012; Tavares et al., 2020), and a few reports describe biofilm formation by L. garvieae isolated from cheese (Akoğlu, 2020; Didienne et al., 2012). The isolates from California and Washington used in this study exhibited robust biofilm formation using the MBEC™ system.…”

Improving Human Health with Milk Fat Globule Membrane, Lactic Acid Bacteria, and Bifidobacteria

“…For example, Lactobacillus can produce substances with antimicrobial activity with an inhibitory effect against pathogenic enteric bacteria [ 53 ]. LAB and bifidobacteria are essential for the health of the host by their direct involvement in metabolism, digestion, and preservation of the immune system [ 54 ]. Both LAB and bifidobacteria are found as part of the human milk microbiome.…”

Oral Immunization of Mice with Cell Extracts from Recombinant Lactococcus lactis Expressing SARS-CoV-2 Spike Protein

“…L. lactis is generally recognized as safe (GRAS) status by the Food and Drug Administration (FDA) [ 29 ]. L. lactis IL1403 is known as a strain widely used for recombinant protein production in laboratory [ 30 ], and there has been no evidence to date that metabolites of L. lactis IL1403 are toxic to experimental animals, which can directly use their cell extracts without purification process. Moreover, in this study, antigens produced from L. lactis induced immune response and did not cause critical changes in the gut microbiome in mice.…”