S-layer protein 2 of vaginal Lactobacillus crispatus 2029 enhances growth, differentiation, VEGF production and barrier functions in intestinal epithelial cell line Caco-2

Int J Biol Macromol. 2021 Oct 31:189:410-419. doi: 10.1016/j.ijbiomac.2021.08.150. Epub 2021 Aug 24.

Abstract

We have previously demonstrated the ability of the human vaginal strain Lactobacillus crispatus 2029 (LC2029) for strong adhesion to cervicovaginal epithelial cells, expression of the surface layer protein 2 (Slp2), and antagonistic activity against urogenital pathogens. Slp2 forms regular two-dimensional structure around the LC2029 cells,which is secreted into the medium and inhibits intestinal pathogen-induced activation of caspase-9 and caspase-3 in the human intestinal Caco-2 cells. Here, we elucidated the effects of soluble Slp2 on adhesion of proteobacteria pathogens inducing necrotizing enterocolitis (NEC), such as Escherichia coli ATCC E 2348/69, E. coli ATCC 31705, Salmonella Enteritidis ATCC 13076, Campylobacter jejuni ATCC 29428, and Pseudomonas aeruginosa ATCC 27853 to Caco-2 cells, as well as on growth promotion, differentiation, vascular endothelial growth factor (VEGF) production, and intestinal barrier function of Caco-2 cell monolayers. Slp2 acts as anti-adhesion agent for NEC-inducing proteobacteria, promotes growth of immature Caco-2 cells and their differentiation, and enhances expression and functional activity of sucrase, lactase, and alkaline phosphatase. Slp2 stimulates VEGF production, decreases paracellular permeability, and increases transepithelial electrical resistance, strengthening barrier function of Caco-2 cell monolayers. These data support the important role of Slp2 in the early postnatal development of the human small intestine enterocytes.

Keywords: Enterocytes; Lactobacilli; S-layer.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Bacterial Adhesion / drug effects
  • Caco-2 Cells
  • Cell Differentiation* / drug effects
  • Cell Membrane Permeability / drug effects
  • Cell Proliferation / drug effects
  • Electric Impedance
  • Enterocytes / drug effects
  • Enterocytes / metabolism*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Lactase / genetics
  • Lactase / metabolism
  • Lactobacillus crispatus / chemistry*
  • Membrane Glycoproteins / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sucrase / genetics
  • Sucrase / metabolism
  • Vagina / microbiology*
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • Membrane Glycoproteins
  • RNA, Messenger
  • S-layer proteins
  • Vascular Endothelial Growth Factor A
  • Alkaline Phosphatase
  • Lactase
  • Sucrase