Prevention of gastrointestinal lead poisoning using recombinant Lactococcus lactis expressing human metallothionein-I fusion protein
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Published on: July 21, 2011
Xue Xiao1, Changbin Zhang1,2, Dajun Liu1
1Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, P.R. China.
Insights
This study developed a genetically engineered bacterium, Lactococcus lactis expressing GST-SUMO-MT, to prevent lead poisoning. Oral administration of this probiotic effectively reduced lead absorption and toxicity in rats, offering a novel gastrointestinal prevention strategy.
Area of Science:
- Biotechnology
- Environmental Health
- Microbiology
Background:
- Low-level lead poisoning is a global health issue affecting millions of children, causing biochemical and neurological damage.
- Preventing lead absorption through the gastrointestinal tract is a key strategy for mitigating lead poisoning.
- A novel biomaterial is needed to effectively block lead uptake in the digestive system.
Purpose of the Study:
- To construct a recombinant Lactococcus lactis strain expressing a fusion protein for lead binding.
- To evaluate the lead-binding capacity and thermodynamic properties of the fusion protein.
- To assess the efficacy of the engineered strain in preventing lead poisoning in a rat model.
Main Methods:
- Construction of recombinant Lactococcus lactis pGSMT/MG1363 expressing glutathione S-transferase (GST)-small molecule ubiquitin-like modifier protein (SUMO)-metallothionein-I (GST-SUMO-MT).
- Thermodynamic analysis of lead binding to GST-SUMO-MT.
- Determination of the lead-binding capacity of the engineered bacterial strain.
- Oral administration of the engineered strain to rats treated with lead acetate, followed by analysis of blood lead levels, liver function, and serum testosterone.
Main Results:
- The fusion protein GST-SUMO-MT demonstrated a high affinity for lead, with an average binding of 3.655 lead molecules per protein.
- The engineered strain pGSMT/MG1363 exhibited a significant lead-binding capacity of 4.11 ± 0.15 mg/g dry mass.
- Oral administration of pGSMT/MG1363 inhibited lead-induced increases in blood lead levels, hepatic dysfunction, and decreased testosterone concentrations in rats.
- No adverse effects on essential mineral ion concentrations (calcium, magnesium, potassium, sodium) were observed.
Conclusions:
- The recombinant Lactococcus lactis strain pGSMT/MG1363 is a promising biomaterial for preventing lead poisoning.
- This engineered probiotic effectively blocks lead absorption in the gastrointestinal tract.
- The study presents a convenient, economical, and safe approach for lead poisoning prevention.
Abstract:
Low-level lead poisoning is an insidious disease that affects millions of children worldwide, leading to biochemical and neurological dysfunctions. Blocking lead uptake via the gastrointestinal tract is an important prevention strategy. With this in mind, we constructed the recombinant Lactococcus lactis strain pGSMT/MG1363, which constitutively expressed the fusion protein glutathione S-transferase (GST)-small molecule ubiquitin-like modifier protein (SUMO)-metallothionein-I (GST-SUMO-MT). The thermodynamic data indicated that the average number of lead bound to a GST-SUMO-MT molecule was 3.655 and this binding reaction was a spontaneous, exothermic and entropy-increasing process. The total lead-binding capacity of pGSMT/MG1363 was 4.11 ± 0.15 mg/g dry mass. Oral administration of pGSMT/MG1363 (1 × 10(10) Colony-Forming Units) to pubertal male rats that were also treated with 5 mg/kg of lead acetate daily significantly inhibited the increase of blood lead levels, the impairment of hepatic function and the decrease of testosterone concentration in the serum, which were all impaired in rats treated by lead acetate alone. Moreover, the administration of pGSMT/MG1363 for 6 weeks did not affect the serum concentration of calcium, magnesium, potassium or sodium ions. This study provides a convenient and economical biomaterial for preventing lead poisoning via the digestive tract.
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