| Autor: |
Panteleev PV; M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia., Safronova VN; M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia., Kruglikov RN; M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia., Bolosov IA; M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia., Bogdanov IV; M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia., Ovchinnikova TV; M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, 117997 Moscow, Russia. |
| Abstrakt: |
Over recent years, a growing number of bacterial species have become resistant to clinically relevant antibiotics. Proline-rich antimicrobial peptides (PrAMPs) having a potent antimicrobial activity and a negligible toxicity toward mammalian cells attract attention as new templates for the development of antibiotic drugs. Here, we mined genomes of all living Camelidae species and found a novel family of Bac7-like proline-rich cathelicidins which inhibited bacterial protein synthesis. The N -terminal region of a novel peptide from the alpaca Vicugna pacos named VicBac is responsible for inhibition of bacterial protein synthesis with an IC 50 value of 0.5 µM in the E. coli cell-free system whereas the C -terminal region allows the peptide to penetrate bacterial membranes effectively. We also found that the full-length VicBac did not induce bacterial resistance after a two-week selection experiment, unlike the N -terminal truncated analog, which depended on the SbmA transport system. Both pro- and anti-inflammatory action of VicBac and its N -terminal truncated variant on various human cell types was found by multiplex immunoassay. The presence of the C-terminal tail in the natural VicBac does not provide for specific immune-modulatory effects in vitro but enhances the observed impact compared with the truncated analog. The pronounced antibacterial activity of VicBac, along with its moderate adverse effects on mammalian cells, make this molecule a promising scaffold for the development of peptide antibiotics. |
