Influence of ZP2 peptide, a synthetic analogue of the GM-GSF active center on the anticytokine activity of bacteria from <i>Enterococcus</i> genus and their ability to produce cytokine-like substances

Abstract

Peptide ZP2, a synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF), exhibits a wide range of immunobiological effects, including antibacterial activity. At the same time, its effect (in sub-inhibitory concentrations) on the biological properties of Enterococcus spp., the causative agents of many infectious and inflammatory diseases remains poorly understood. The aim of our study was to analyze the nature of the effect of synthetic peptide ZP2 on anticytokine activity (ACA) and its ability to produce cytokine-like substances (CLS) in Enterococcus spp. 18 clinical isolates of Enterococcus spp. were used. Over the experiments, the bacterial strains were cultured in Schaedlers broth with ZP2 peptide at 37 C for 24 hours. No specific peptide was added in the control. ACA for IL-8, TNF and IL-17A and the production of the corresponding CLS were determined by the ELISA method. To assess ACA, the proportion of cytokine inactivation in the experiment relative to the control was calculated and expressed in pg/ml; CLS production was evaluated by the level of cytokines in the experiment and control, expressed as pg/ml. The data were subjected to statistical processing. It was revealed that Enterococcus spp. strains are capable of secreting compounds that inactivate cytokines IL-8, IL-17A and TNF, and produce CLS in the culture medium. Intragenital and intraspecific variability was noted in the presence and frequency of occurrence and in the severity of these properties. It was found that the ZP2 peptide in E. faecium increases ACA with respect to all studied cytokines. When tested with E. faecalis, it either did not affect their ACA against TNF and IL-8, or completely inhibited ACA for IL-17A. At the same time, ZP2 blocked the production of CLS, e.g., IL-17A and IL-8 in E. faecium, but increased the production of CLS similar to TNF, and, with E. faecalis, it increased the number of IL-17A-producing isolates twofold, although the average level of production of these CLS was lower than in the control. Enterococcus spp strains are capable of secreting compounds that inactivate cytokines IL-8, TNF and IL- 17A, and may produce substances similar to these cytokines. The synthetic peptide ZP2 has a modifying effect on the manifestation of these properties by Enterococci. Further studies of biological and pathogenetic features of Enterococci and other bacterial species, as well as modifying effects of the ZP2 peptide are required.