Plasmid-Based Gene Expression Systems for Lactic Acid Bacteria: A Review

Abstract

Lactic acid bacteria (LAB) play a very vital role in food production, preservation, and as probiotic agents. Some of these species can colonize and survive longer in the gastrointestinal tract (GIT), where their presence is crucially helpful to promote human health. LAB has also been used as a safe and efficient incubator to produce proteins of interest. With the advent of genetic engineering, recombinant LAB have been effectively employed as vectors for delivering therapeutic molecules to mucosal tissues of the oral, nasal, and vaginal tracks and for shuttling therapeutics for diabetes, cancer, viral infections, and several gastrointestinal infections. The most important tool needed to develop genetically engineered LABs to produce proteins of interest is a plasmid-based gene expression system. To date, a handful of constitutive and inducible vectors for LAB have been developed, but their limited availability, host specificity, instability, and low carrying capacity have narrowed their spectrum of applications. The current review discusses the plasmid-based vectors that have been developed so far for LAB; their functionality, potency, and constraints; and further highlights the need for a new, more stable, and effective gene expression platform for LAB.

Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice

“…In recent years, numerous studies have shown that LAB exhibit a potential role in delivering biologically active molecules, and therefore promoting the development of mucosal vaccine (Levit et al., 2022 ). To date, various plasmid-based gene expression systems for LAB have been established, and this highly expands the uses of LAB as drug delivery vehicles through genetic modification (Kazi et al., 2022 ). However, using these genetically modified organisms may raise significant public and political concerns.…”

Characterization of a novel theta-type replicon of indigenous plasmid pTE15 from Lactobacillus reuteri N16

“…This study describes the characterization of pTE15 and showed that this large, naturally occurring plasmid (~ 15-kb) replicates via another theta mode mechanism. To our knowledge, although the characteristics of six theta-type plasmids belonged to lactobacilli were description thus for [ 20 – 24 ], but they almost could be classified as class A replicon, which must the plasmid encoded the Rep protein with a related origin of replication and replicate independently of DNA polymerase I [ 25 ]. Therefore, this is the first study demonstrating an unclassified class replicon of theta plasmid in a Lactobacillus species.…”

“…To date, the theta-type replication plasmid in lactobacilli were including pLP60 [ 20 ], pRC12 and pRC18 [ 21 ], pRV500 [ 22 ], pREN [ 23 ], and pLJ1 [ 24 ], especially the pRC12, pRC18, pRV500, and pREN belonged to the pUCL287 subfamily. They were class A of theta replicons that must plasmid encoded Rep protein with a related origin of replication and replicate independently of DNA pol I.…”

Enhancing the Effect of Nucleic Acid Vaccines in the Treatment of HPV-Related Cancers: An Overview of Delivery Systems

“…These organisms also benefit the administration route via the mucosal route that beneficially induces mucosal and systemic immune responses [176]. LABs, for example, are even more suitable because, in addition to being non-pathogenic, withstanding acidic conditions in the gastrointestinal (GI) system, and protecting nucleic acids, they also exhibit probiotic effects [189]. In addition to these, bacterial derivatives can be used as potentially useful nanocarriers for antigen delivery, some as "bacterial ghosts" that possess the ability to stimulate immune responses as potent as those of live bacteria [190].…”