Recombinant Human Peptidoglycan Recognition Proteins Reveal Antichlamydial Activity

Infect Immun. 2016 Jun 23;84(7):2124-2130. doi: 10.1128/IAI.01495-15. Print 2016 Jul.

Abstract

Peptidoglycan recognition proteins (PGLYRPs) are innate immune components that recognize the peptidoglycan and lipopolysaccharides of bacteria and exhibit antibacterial activity. Recently, the obligate intracellular parasite Chlamydia trachomatis was shown to have peptidoglycan. However, the antichlamydial activity of PGLYRPs has not yet been demonstrated. The aim of our study was to test whether PGLYRPs exhibit antibacterial activity against C. trachomatis Thus, we cloned the regions containing the human Pglyrp1, Pglyrp2, Pglyrp3, and Pglyrp4 genes for subsequent expression in human cell lines. We obtained stable HeLa cell lines that secrete recombinant human PGLYRPs into culture medium. We also generated purified recombinant PGLYRP1, -2, and -4 and confirmed their activities against Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria. Furthermore, we examined the activities of recombinant PGLYRPs against C. trachomatis and determined their MICs. We also observed a decrease in the infectious ability of chlamydial elementary bodies in the next generation after a single exposure to PGLYRPs. Finally, we demonstrated that PGLYRPs attach to C. trachomatis elementary bodies and activate the expression of the chlamydial two-component stress response system. Thus, PGLYRPs inhibit the development of chlamydial infection.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / pharmacology*
  • Cell Line
  • Chlamydia Infections / drug therapy
  • Chlamydia Infections / microbiology*
  • Chlamydia trachomatis / drug effects*
  • Chlamydia trachomatis / genetics
  • Gene Expression Regulation, Bacterial / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Carrier Proteins
  • Recombinant Fusion Proteins
  • peptidoglycan recognition protein