Bioengineered Probiotics: Synthetic Biology Can Provide Live Cell Therapeutics for the Treatment of Foodborne Diseases

Abstract

The rising prevalence of antibiotic resistant microbial pathogens presents an ominous health and economic challenge to modern society. The discovery and large-scale development of antibiotic drugs in previous decades was transformational, providing cheap, effective treatment for what would previously have been a lethal infection. As microbial strains resistant to many or even all antibiotic drug treatments have evolved, there is an urgent need for new drugs or antimicrobial treatments to control these pathogens. The ability to sequence and mine the genomes of an increasing number of microbial strains from previously unexplored environments has the potential to identify new natural product antibiotic biosynthesis pathways. This coupled with the power of synthetic biology to generate new production chassis, biosensors and “weaponized” live cell therapeutics may provide new means to combat the rapidly evolving threat of drug resistant microbial pathogens. This review focuses on the application of synthetic biology to construct probiotic strains that have been endowed with functionalities allowing them to identify, compete with and in some cases kill microbial pathogens as well as stimulate host immunity. Weaponized probiotics may have the greatest potential for use against pathogens that infect the gastrointestinal tract: Vibrio cholerae, Staphylococcus aureus, Clostridium perfringens and Clostridioides difficile. The potential benefits of engineered probiotics are highlighted along with the challenges that must still be met before these intriguing and exciting new therapeutic tools can be widely deployed.

About Functional Foods: The Probiotics and Prebiotics State of Art

“…Indeed, the intragastric administration of Lactococcus lactis , which secrete IL-10, reduces or prevents the dextran sulfate sodium- (DSS) induced colitis in IL-10 deficient mice. Finally, it has been demonstrated that L. lactis that is secreting the LcrV protein ( Y. Pseudotuberculosis -protein) in a pseudotuberculosis mouse model has a protective role against the onset of colitis [ 101 , 102 , 103 ].…”

Recombinant Probiotic Preparations: Current State, Development and Application Prospects

“…rhamnosus, Lcb. casei, and S. boulardii, either alone or together with antibiotic therapy, showed some treatment success in living models [112]. Today, there are studies on the creation of recombinant strains based on Lb.…”

“…The creation of a vaccine against Clostridium perfringens infection (the causative agent of necrotizing enterocolitis) and other gastrointestinal tract diseases is being considered. The need to create a vaccine against this pathogen is due to its resistance to standard antibiotics and the belief that vaccination is more effective [112]. Lcb.…”

“…3) resistance to pathogens and the acquisition of new forms or resistance due to the formation of biofilms or changes in signaling molecules; 4) emergence of the problem of biocontamination with new "artificial" microorganisms [82,112].…”

“…In addition, recombinant probiotics in most cases are tested in animal models and full clinical use requires further improvements and studies [11,112]. Although the use of genetically modified probiotics as biotherapeutic agents is not approved today, such microorganisms still have a practical value, e.g., as a "cell factory" for the synthesis of food components or enzymes.…”