Correspondence to Author:  Elena V. Navolotskaya, 

Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Science Avenue, 6, Pushchino, Moscow Region, 142290 Russian Federation.

Abstract:

In the present study we investigated the activity of the synthetic peptide LKEKK (Np5) in murine model of tuberculosis induced by Mycobacterium bivis-bovinus 8 strain. Therapy with Np5 at doses of 0.01, 0.1, and 1 µg/kg (5 daily injections) decreased the lung damage index compared to untreated controls and to those treated with isoniazid alone. The growth of M. bivis-bovinus 8 in spleen culture was decreased. Study of cytokine production showed that on the 24th day after treatment with Np5 the secretion of IL-2 was restored to the level seen in uninfected animals. IFN-γ production be both thymus and spleen cells, as well as its circulating levels in serum, was increased by the Np5 treatment. Concurrently, IL-4 production was decreased in the same cell types and in the serum. The Np5 treatment also stimulated the macrophage functions, which had been decreased by tuberculosis infection and isoniazid therapy, with an improved phagocytosis activity of peritoneal macrophages. Thus, the Np5 treatment increased the efficacy of anti-tuberculosis therapy as well as strength of the immune response.

Keywords:Protein: Peptide; Receptor; Cytokine; Tuberculosis

Introduction: 
Tuberculosis is a widespread in the world chronic infectious disease of humans and animals, which is caused by various types of mycobacteria from the Mycobacterium tuberculosis complex group (M. tuberculosis, M. bovis, M. africanum, M. microti, M. canettii); it causes more than 1.5 million deaths annually (Churchyard et al., 2017; Furin et al., 2019; Natarajan et al., 2020). Experts note that over the past few decades, drug resistance of mycobacterial strains has increased significantly. Currently, patients are increasingly becoming infected with strains of mycobacteria that are resistant to almost all antibiotics, that requires an urgent search for new drugs and treatment methods (Jacobo-Delgado et al., 2023). A unique feature of mycobacteria is the complexity of its cell wall. This structure consists of a plasma membrane, a cell wall core and an outer envelope, including many complex lipids, peptidoglycans and mycoic acids. (Grzegorzewicz et al., 2016; Chiaradia et al., 2017; Singh et al., 2018; Stokas et al., 2020). Mycolic acids, long-chain branched fatty acids, containing 60- 90 carbon atoms per molecule, are an exclusive component of the cell wall of mycobacteria; they make the surface of the bacilli waxy and highly hydrophobic, providing protection against hydrophilic antibiotics, oxidative damage and the host immune response (Singh et al., 2017). Several years ago we synthesized the peptide LKEKK corresponding to the sequences 16–20 of human thymosin-α1 (TM-α1) and 131–135 of interferon-α2 (IFN-α2) and showed that it binds with high affinity to murine macrophage-like cells of line RAW 264.7. In the 10–1000 nM concentration range, the peptide dose-dependently increased the nitric oxide (NO) production, the activity of soluble guanylate cyclase (sGC), as well as the adhesion, spreading, and capacity to digest bacteria of Salmonella typhimurium virulent strain 415 in vitro by the cells . The synthetic peptide with inverted KKEKL sequence tested in parallel was inactive. Thus, the peptide LKEKK binding to RAW 264.7 cells leads to an increase in NO-synthase, guanylate cyclase and phagocytic activity (Navolotskaya et al., 2019). The purpose of this work is to study the effect of the peptide LKEKK (Np5) on a mouse model of tuberculosis.

Citation:

Elena V. Navolotskaya. Action of Synthetic Peptide LKEKK in Experimental Tuberculosis. Journal of Immunology 2024.