Probiotic engineering: towards development of robust probiotic strains with enhanced functional properties and for targeted control of enteric pathogens

Abstract

There is a growing concern about the increase in human morbidity and mortality caused by foodborne pathogens. Antibiotics were and still are used as the first line of defense against these pathogens, but an increase in the development of bacterial antibiotic resistance has led to a need for alternative effective interventions. Probiotics are used as dietary supplements to promote gut health and for prevention or alleviation of enteric infections. They are currently used as generics, thus making them non-specific for different pathogens. A good understanding of the infection cycle of the foodborne pathogens as well as the virulence factors involved in causing an infection can offer an alternative treatment with specificity. This specificity is attained through the bioengineering of probiotics, a process by which the specific gene of a pathogen is incorporated into the probiotic. Such a process will subsequently result in the inhibition of the pathogen and hence its infection. Recombinant probiotics offer an alternative novel therapeutic approach in the treatment of foodborne infections. This review article focuses on various strategies of bioengineered probiotics, their successes, failures and potential future prospects for their applications.

The global preclinical antibacterial pipeline

“…There is a trend towards reducing the complexity of faecal transplants by controlling the transfer of bacterial strains or selecting natural strains derived from a healthy microbiota 59,60 . New techniques based on synthetic biology and systems biology allow the precise genetic engineering of well-known probiotics 61 , which may also express specific antibacterial substances [62][63][64] . A long-known strategy to maintain a healthy microbiota is the use of antibiotic inactivators or absorbers of bacterial toxins in the gut.…”

The Inoculation of Probiotics In Vivo Is a Challenge: Strategies to Improve Their Survival, to Avoid Unpleasant Changes, or to Enhance Their Performances in Beverages

“…The performance of probiotic strains can be improved by bioengineering, that is, the manipulation of a gene to improve the tolerance to technological stress, including but not limited to temperature extremes, oxygen and acidification, during food production, and/or survival of the probiotic in the gut, to confer beneficial effects to the host [68].…”

“…One of the main drawbacks of working with bioengineered probiotics is that they are classified as genetically modified organisms (GMOs) [68]. Engineered probiotics contain additional elements for inducing antigenicity and immunomodulation; however, these changes could also affect metabolic pathways and safety [69].…”

“…Increased resistance to some solvents Inhibition of adhesion of Listeria to host cells [68] Lb. salivarius Increased resistance to several stresses [68] Lb. jensenii Inhibition of HIV in CD4 + cells and macrophages [69] Lb.…”

Coopting the Lap system ofPseudomonas fluorescensto reversibly customize bacterial cell surfaces

“…Such beneficial roles include competitively excluding pathogen colonization (3), bioelectricity generation (4), and enhancing bioleaching (5, 6). Furthermore, recent microbiome research cataloging various beneficial relationships between bacterial biofilms and their human host has caused a for therapeutic purposes (7). One goal of synthetic biology is to program bacterial cell surfaces to perform customized functions under an exclusive set of environmental conditions, such as binding a defined surface or remediating a toxic metal from an environment.…”