Evaluation of Antimicrobial Activity of the C3f Peptide, a Derivative of Human C3 Protein

• Published in: Russian journal of bioorganic chemistry 2021-05, Vol.47 (3), p.741-748
• Main Authors: Pozolotin, V. A., Umnyakova, E. S., Kopeykin, P. M., Komlev, A. S., Dubrovskii, Y. A., Krenev, I. A., Shamova, O. V., Berlov, M. N.
• Format: Article
• Language: English
• Subjects: Antiinfectives and antibacterials; Antimicrobial agents; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Chemical bonds; Complement; Covalent bonds; E coli; Gram-positive bacteria; Life Sciences; Listeria; Microorganisms; Organic Chemistry; Peptides; Proteins; Solid phase synthesis
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162021030158

The complement system plays an important role in the protection of the organism from infection. A key step in complement activation is the proteolytic cleavage of C3 protein resulting in a soluble anaphylatoxin C3a peptide and C3b protein that is able to form a covalent bond with surface molecules of microbial cells. The activity of C3b is regulated by its subsequent limited proteolysis with the release of the C3f peptide, which is believed to have no functional activity itself. Based on the physicochemical properties of C3f, we hypothesized that this peptide may exhibit antimicrobial activity. Complement activation usually takes place on the surface of pathogens, in particular, bacterial cells, and local generation of antimicrobial peptides can contribute significantly to their neutralization. The antimicrobial activity of complement derivatives, C3a and C4a peptides, is already known from the literature. To study the antimicrobial properties of C3f, we obtained this peptide by the method of solid-phase synthesis. It has been shown that human C3f exhibits moderate antimicrobial activity in vitro against certain gram-positive bacteria ( Listeria monocytogenes , Micrococcus luteus , Enterococcus faecium ) with minimal inhibitory concentrations of 70 μM (for L. monocytogenes ) or higher. The revealed antimicrobial activity of C3f is much lower than the activity of C3a described in the literature. Several microorganisms ( Bacillus cereus , Escherichia coli , Candida albicans ) were resistant to C3f.