O.V. Galzitskaya1*, S.Yu. Grishin1, A.V. Glyakina1, M.V. Slizen1, A.V. Panfilov1, P.A. Domnin2,3, A.P. Kochetov4,5, A.A. Surin6, S.V. Kravchenko7, A.K. Surin5, S.A. Ermolaeva2
1Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Russia
2Gamaleya Research Centre of Epidemiology and Microbiology, 123098 Moscow, Russia
3Biology Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia
4Pushchino State Institute of Natural Sciences, Pushchino, Moscow Region 142290, Russia
5The Branch of the Institute of Bioorganic Chemistry, Pushchino, Russia
6Faculty of Applied math, MIREA – Russian Technological University, Moscow, 119454 Russia
7Institute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, 625003 Tyumen, Russia
ogalzit [at] vega.protres.ru
Abstract
One of the reasons for the mortal danger to humans is the ability of pathogenic bacteria to form biofilms. The formation of biofilms is an evolutionarily conservative defense mechanism against adverse conditions. The use of this protection by pathogenic bacteria reduces the effectiveness of the main means of combating them – antibiotics, which complicates the production of new types of drugs. There are two types of antimicrobial agents that are not known antibiotics: nanoparticles and antimicrobial peptides. We demonstrated that peptides synthesized based on the amino acid sequence of proteins and capable of amyloid formation and coaggregation with the whole protein exhibit antimicrobial activity. The ability of peptides to coaggregate with target proteins can help combat biofilm-forming bacterial communities.
We evaluated the antimicrobial effects of ten synthesized hybrid peptides, which were obtained based on the sequences of the S1 ribosomal protein of P. aeruginosa and S. aureus. It is important that some peptides demonstrated high antimicrobial activity comparable to the antibiotic gentamicin sulfate against pathogenic strains of MRSA, S. aureus, and P. aeruginosa. These peptides showed no toxicity to eukaryotic cells. Our study demonstrates the promise of hybrid peptides based on the amyloidogenic regions of the S1 ribosomal protein for the development of new antimicrobials against Gram-positive and Gram-negative bacteria resistant to traditional antibiotic.
Keywords: amyloid, coaggregation, antimicrobial peptides
Acknowledgement: This research was funded by the Russian science foundation, Grant Number 18-14-00321.
