Antibacterial properties of tuftsin and its analogs

Abstract

The antibacterial properties of tuftsin and its 11 analogs on 20 bacterial strains were investigated. Tuftsin showed a definite antibacterial effect at a minimal effective concentration of 62.5 ,ug/ml. All analogs were either less effective or lacked any activity. The bacteria used included some highly pathogenic organisms.The tetrapeptide tuftsin (Thr-Lys-Pro-Arg) was discovered and isolated by Najar et al. (11,15,16) in 1973 on the basis of its ability to stimulate the phagocytic activity of polymorphonuclear granulocytes and macrophages. The broad spectrum of the biological activities of tuftsin has been presented in several communications (5,10,(12)(13)(14)17). Besides phagocytosis stimulation, other activities include stimulation of (i) motility of granulocytes, (ii) humoral antibody formation, and (iii) tumoricidal activity of phagocytic cells as well as bacterial killing properties. It also exhibits analgesic properties.In this communication, we reported an investigation of the antibacterial activities of tuftsin and its analogs that were modified in position 3 of the peptide chain: Thr-Lys-HisArg, Thr-Lys-Gly-Arg, Thr-Lys-Ser-Arg, Thr-Lys-Phe-Arg, Thr-Lys-Asp-Arg, Thr-Lys-Ile-Arg, Thr-Lys-Sar-Arg, ThrLys-Tyr-Arg, Thr-Lys-Thr-Arg, Thr-Lys-Arg-Arg, and ThrLys-Gln-Arg (Table 1).We have shown earlier (7,8) that most of these tetrapeptides stimulated phagocytosis to a high degree. In particular (10) have reported that macrophages incubated in the presence of tuftsin exhibit bactericidal activity on several bacteria, including Listeria monocytogenes. It is to be noted that tuftsin and its analogs used here possess strongly basic characters. In this connection, it is known that basic peptides such as diand tripeptide derivatives of L-lysine (2, 4), L-ornithine (1), and the pentapeptide Lys-Lys-Thr-Lys-D-Leu and its Ndecanoyl derivative (9) show very strong activities against various bacterial species. On this basis, our objective was to ascertain whether tuftsin and its analogs could display any antibacterial activity directly in bacteria cultures. MATERIALS AND METHODSAll tetrapeptides were synthesized as previously reported (6)(7)(8) nas aeruginosa WSRO 109, Bortedella bronchoseptica NCTC 8344, and Serratia marcescens PCM 501. The culture medium was a ready-to-use Difco broth. Preparation of the culture medium was carried out as described before (2, 4).The antibacterial activities of tuftsin and its 11 analogs were assessed by a standard dilution method in an appropriate test medium. The initial concentration of standard solution in water was 10 mg/ml. The concentrations of working solutions prepared in the test media were 1,000, 500, 250, 125, 62.5, 31.25, 15.6, and 3.9 p,g/ml. To the geometrical series of the solutions, 1 ml of each standardized suspension of microorganisms was added. Samples with bacteria were incubated for 24 h at 37°C. After incubation, the minimal inhibitory concentrations (MICs) were determined in terms of concentration of the compound at which the sample became turbid. For each com...

Tuftsin: a natural molecule against SARS-CoV-2 infection

“…When the concentration reached 625 μ M, the combination of SARS-CoV-2 S1 and ACE2 was completely blocked. It has been confirmed that a 156 μM concentration of tuftsin can exist at a high concentration in the internal environment after intravenous injection 28 . We conceive that tuftsin can be designed as an oral or nasal spray.…”

Tuftsin: A Natural Molecule Against SARS-CoV-2 Infection

“…It is worth noting that there exists a group of asymptomatic carriers or mild symptoms’ individuals during the pandemic ( Schijns and Lavelle, 2020 ; Boyton and Altmann, 2021 ). As tuftsin has anti-infection and anti-inflammatory properties ( Blok-Perkowska et al, 1984 ; Thompson et al, 2018 ), it is possible that asymptomatic individuals have higher content of tuftsin.…”

Quantum Density Functional Theory Studies on Additive Hydration of Tuftsin Tetrapeptide

“…In addition, tuftsin shows antitumor activity [5], and it can be used as an activator of macrophages in cancer treatment [6], and it is supposed that tuftsin deficiency leads to the risk of bacterial infection in HIVpositive patients [7]. Apart from the above natal significance, because of the broad spectrum of the other biological activities such as mobility of granulocytes, humoral antibody formation, and tumoricidal activity of phagocytic cells as well as bacterial killing properties [8], tuftsin has been considered as the subject of several theoretical and experimental studies with a view to analyze its structure-activity relationships.…”

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