Prevention of gastrointestinal lead poisoning using recombinant Lactococcus lactis expressing human metallothionein-I fusion protein

Sci Rep. 2016 Apr 5:6:23716. doi: 10.1038/srep23716.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Brain / drug effects
  • Calorimetry
  • Disease Models, Animal
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / microbiology
  • Genetic Vectors
  • Glutathione Transferase / metabolism
  • Humans
  • Intestines / drug effects
  • Kidney / drug effects
  • Lactococcus lactis / metabolism*
  • Lead / adverse effects*
  • Lead Poisoning / prevention & control*
  • Liver / drug effects
  • Male
  • Metallothionein / biosynthesis*
  • Muscle, Skeletal / drug effects
  • Plasmids / metabolism
  • Rats
  • Recombinant Proteins / biosynthesis*
  • Testis / drug effects
  • Thermodynamics
  • Tissue Distribution

Substances

  • Recombinant Proteins
  • Lead
  • Metallothionein
  • Glutathione Transferase