Antimicrobial and Amyloidogenic Activity of Peptides Synthesized on the Basis of the Ribosomal S1 Protein from Thermus Thermophilus

Int J Mol Sci. 2020 Sep 2;21(17):6382. doi: 10.3390/ijms21176382.

Abstract

Controlling the aggregation of vital bacterial proteins could be one of the new research directions and form the basis for the search and development of antibacterial drugs with targeted action. Such approach may be considered as an alternative one to antibiotics. Amyloidogenic regions can, like antibacterial peptides, interact with the "parent" protein, for example, ribosomal S1 protein (specific only for bacteria), and interfere with its functioning. The aim of the work was to search for peptides based on the ribosomal S1 protein from T. thermophilus, exhibiting both aggregation and antibacterial properties. The biological system of the response of Gram-negative bacteria T. thermophilus to the action of peptides was characterized. Among the seven studied peptides, designed based on the S1 protein sequence, the R23I (modified by the addition of HIV transcription factor fragment for bacterial cell penetration), R23T (modified), and V10I (unmodified) peptides have biological activity that inhibits the growth of T. thermophilus cells, that is, they have antimicrobial activity. But, only the R23I peptide had the most pronounced activity comparable with the commercial antibiotics. We have compared the proteome of peptide-treated and intact T. thermophilus cells. These important data indicate a decrease in the level of energy metabolism and anabolic processes, including the processes of biosynthesis of proteins and nucleic acids. Under the action of 20 and 50 μg/mL R23I, a decrease in the number of proteins in T. thermophilus cells was observed and S1 ribosomal protein was absent. The obtained results are important for understanding the mechanism of amyloidogenic peptides with antimicrobial activity and can be used to develop new and improved analogues.

Keywords: amyloidogenic regions; antibacterial peptides; mass spectrometry; proteome; ribosomal S1 proteins; toxicity.

MeSH terms

  • Amino Acid Sequence
  • Amyloidogenic Proteins / metabolism*
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Peptide Fragments / pharmacology*
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / metabolism*
  • Skin / cytology*
  • Skin / drug effects
  • Thermus thermophilus / growth & development
  • Thermus thermophilus / metabolism*

Substances

  • Amyloidogenic Proteins
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Peptide Fragments
  • Ribosomal Proteins
  • ribosomal protein S1