Inhibition of Shigella flexneri-induced transepithelial migration of polymorphonuclear leucocytes by cadaverine

Cell Microbiol. 1999 Sep;1(2):143-55. doi: 10.1046/j.1462-5822.1999.00014.x.

Abstract

Dysentery caused by Shigella species is characterized by infiltration of polymorphonuclear leucocytes (PMNs) into the colonic mucosa. Shigella spp. evolved into pathogens by the acquisition of virulence genes and by the deletion of 'antivirulence' genes detrimental to its pathogenic lifestyle. An example is cadA (encoding lysine decarboxylase), which is uniformly absent in Shigella spp., whereas it is present in nearly all isolates of the closely related non-pathogen Escherichia coli. Here, using monolayers of T84 cells to model the human intestinal epithelium, we determined that the introduction of cadA into S. flexneri and the expression of lysine decarboxylase attenuated the bacteria's ability to induce PMN influx across model intestinal epithelium. Such inhibition was caused by cadaverine generated from the decarboxylation of lysine. Cadaverine treatment of model intestinal epithelia specifically inhibited S. flexneri induction of PMN transepithelial migration, while having no effect on the ability of Salmonella or enteropathogenic E. coli (EPEC) to induce PMN migration. These observations not only provide insight into mechanisms of S. flexneri pathogen evolution and pathogenesis, but also suggest a potential for the use of cadaverine in the treatment of dysentery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Cadaverine / metabolism
  • Cadaverine / pharmacology*
  • Carboxy-Lyases / genetics
  • Carboxy-Lyases / metabolism*
  • Cell Culture Techniques
  • Cell Line
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Polarity
  • Cell Size
  • Dose-Response Relationship, Drug
  • Dysentery
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli O157 / metabolism
  • Humans
  • Interleukin-8 / metabolism
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / microbiology*
  • Lysine / metabolism
  • Membrane Proteins / metabolism
  • Microscopy, Fluorescence
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • Neutrophils / drug effects
  • Neutrophils / physiology*
  • Phosphoproteins / metabolism
  • Salmonella typhimurium / metabolism
  • Shigella flexneri / metabolism
  • Shigella flexneri / pathogenicity*
  • Signal Transduction
  • Zonula Occludens-1 Protein

Substances

  • Actins
  • Interleukin-8
  • Membrane Proteins
  • Phosphoproteins
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • N-Formylmethionine Leucyl-Phenylalanine
  • Carboxy-Lyases
  • lysine decarboxylase
  • Lysine
  • Cadaverine