Recombinant Lactobacillus Expression Strain Construction

The development of Lactic acid bacteria (LAB) expression systems has stimulated studies aimed at determining the cellular localization of expressed antigens and the effect of localization on their immunogenic capacity. Additional studies and clinical trials will facilitate the use of recombinant LAB (RecLAB) as a novel therapeutic approach to the treatment of a wide variety of human diseases in the near future. Creative Biolabs specialized in providing custom live biotherapeutics product (LBP) services and products for researchers around the world.

Overview

LAB has a long history of being used in food production and food preservation. Their safety status, probiotic activities, and capacity to survive the passage through the gastrointestinal tract (GIT) make these bacteria excellent candidates for targeting therapeutic molecules. Most importantly, this approach reduces potential side effects associated with the classical systemic routes of drug delivery. Over the last 20 years, a large number of health benefits of RecLAB, particularly lactococcus and lactobacillus, have been demonstrated. Data obtained in a phase I clinical trial conducted with a recombinant strain of L. lactis secreting human IL-10 showed that the containment strategy used to construct the strain was not only safe and effective but also proved that mucosal delivery of IL-10 by a recLAB is feasible in humans.

RecLAB can deliver widely diverse molecules into the intestine, where they exert various health benefits.Fig.1 RecLAB can deliver widely diverse molecules into the intestine, where they exert various health benefits. (Bermúdez-Humarán, 2013)

LAB Delivery Systems and Advantages as Mucosal Delivery Vehicles

LAB are non-pathogenic microorganism and is considered safer than some attenuated vectors. The recombinant LAB strains can express multiple exogenous proteins, which may facilitate the development of multivalent vaccines. LAB is not only used as live bacteria in mucosal immunity but also effective as mucosal carriers.

Strategies to Display Proteins at the Surface of LAB

Gram-positive bacteria have only one cytoplasmic cell membrane, meaning that protein export only involves one membrane translocation. There are two main ways of immobilizing secreted proteins on bacterial surfaces, one through covalent binding to surface components, and the other through non-covalent binding to membrane or cell wall components through specific binding domains. Expression and export of a heterologous protein containing the desired anchoring signal are at the basis of most display strategies. The success of these steps is a major factor in determining the viability of the recombinant strain and the amount of protein displayed on its surface. The expression, secretion, and surface display of exogenous target proteins have been extensively studied in LAB.

Methods for protein display in lactobacilli.Fig.2 Methods for protein display in lactobacilli. (Michon, 2016)

Recombinant Lactobacillus Expression Strains Construction Services at Creative Biolabs

So far, several recombinant LAB has reached clinical trials. The first clinical study involved the use of Lactobacillus for human IL-10 secretion in patients with Crohn's disease. The treatment proved to be safe and well tolerated, with a reduction in Crohn's disease symptoms. Creative Biolabs is a USA biotech company, we are highly experienced in LBP development. Our team can provide you with the right support and expertise for each of the different stages of the development of your project. If you are interested in our recombinant lactobacillus expression strains construction services, please contact us for more information.

References

  1. Bermúdez-Humarán, L.G.; et al. Engineering lactococci and lactobacilli for human health. Curr Opin Microbiol. 2013 Jun;16(3): 278-83.
  2. Michon, C.; et al. Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications. Microb Cell Fact. 2016 May 3;15: 70.

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