Development of a Stress-Inducible Controlled Expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces

Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity

“…Lactococcus lactis MG1363 containing pGK‐empty plasmid (LL‐WT) or pGroESL‐psgA (LL‐PgsA) plasmids were generated using previously described Materials and Methods (29) detailed in the Supplemental Data. Animals were housed in Anaxem‐Micalis germ‐free rodent facility (INRA, Jouy‐en‐Josas, France) and were orally administered with L. lactis MG1363 containing LL‐psgA or LL‐WT (1 × 10 9 CFU in 200 µl of sterile PBS per gavage) for 4 d.…”

Use of Wild Type or Recombinant Lactic Acid Bacteria as an Alternative Treatment for Gastrointestinal Inflammatory Diseases: A Focus on Inflammatory Bowel Diseases and Mucositis

“…However, the majority of the expression vectors present inherent safety drawbacks due to the necessity to add chemical compounds into the bacterial culture to induce heterologous protein expression prior to in vivo administration. Other food grade expression systems that do not require the pre-induction of the cultures to allow the expression of a given recombinant protein have been reported (Derre et al, 1999; Ruiz et al, 2012; Benbouziane et al, 2013). Benbouziane et al (2013) developed the stress-inducible controlled expression system (SICE), based on the use of the heat shock protein groESL operon promoter (pGroESL) from L. lactis , to deliver proteins of health interest in situ .…”

“…Other food grade expression systems that do not require the pre-induction of the cultures to allow the expression of a given recombinant protein have been reported (Derre et al, 1999; Ruiz et al, 2012; Benbouziane et al, 2013). Benbouziane et al (2013) developed the stress-inducible controlled expression system (SICE), based on the use of the heat shock protein groESL operon promoter (pGroESL) from L. lactis , to deliver proteins of health interest in situ . Heat-shock proteins play an essential role under different stress conditions such as heat-shock, low pH, UV-irradiation, and salt stress.…”

“…Heat-shock proteins play an essential role under different stress conditions such as heat-shock, low pH, UV-irradiation, and salt stress. Indeed, upon administration into the host, recombinant bacteria should find very different conditions from culture conditions and likely suffer different types of stress (Benbouziane et al, 2013). In the case of oral administration, heat stress can be accompanied by an acid stress during passage through the stomach as well as bile stress in the duodenum.…”

Previous Ingestion ofLactococcus lactisby Ethanol-Treated Mice Preserves Antigen Presentation Hierarchy in the Gut and Oral Tolerance Susceptibility

“…Of particular interest among probiotic properties of lactobacilli is their ability to modulate the innate and adaptive pro-inflammatory and anti-inflammatory immunity (Huibregtse et al, 2007). Genetically modified Lactococcus lactis (LL) strains have been employed as a vehicle for antigen delivery to the intestinal environment, aiming at establishing oral tolerance mediated by regulatory T (Treg) cells (Benbouziane et al, 2013;Huibregtse et al, 2007;Jing et al, 2011;LeBlanc et al, 2011;Rezende et al, 2013). Oral administration of LL producers of heat-shock proteins (Hsp65) is able to modulate and prevent inflammatory disorders in experimental models (LeBlanc et al, 2011;Rezende et al, 2013;Zanin-Zhorov et al, 2006), such as the development of MOG35e55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice (Rezende et al, 2013).…”