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Mar Drugs
2018 Oct 02;1610:. doi: 10.3390/md16100366.
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Antimicrobial and Antibiofilm Activity of a Recombinant Fragment of β-Thymosin of Sea Urchin Paracentrotus lividus.
Spinello A
,
Cusimano MG
,
Schillaci D
,
Inguglia L
,
Barone G
,
Arizza V
.
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With the aim to obtain new antimicrobials against important pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, we focused on antimicrobial peptides (AMPs) from Echinoderms. An example of such peptides is Paracentrin 1 (SP1), a chemically synthesised peptide fragment of a sea urchin thymosin. In the present paper, we report on the biological activity of a Paracentrin 1 derivative obtained by recombination. The recombinant paracentrin RP1, in comparison to the synthetic SP1, is 22 amino acids longer and it was considerably more active against the planktonic forms of S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 at concentrations of 50 µg/mL. Moreover, it was able to inhibit biofilm formation of staphylococcal and P. aeruginosa strains at concentrations equal to 5.0 and 10.7 µg/mL, respectively. Molecular dynamics (MD) simulations allowed to rationalise the results of the experimental investigations, providing atomistic insights on the binding of RP1 toward models of mammalian and bacterial cell membranes. Overall, the results obtained point out that RP1 shows a remarkable preference for bacterial membranes, in excellent agreement with the antibacterial activity, highlighting the promising potential of using the tested peptide as a template for the development of novel antimicrobial agents.
Figure 1. RP1 folded structure. The structure of RP1 is divided in three parts, which are shown in three different colours: blue, red, and yellow, respectively, for RP1-1, RP1-2, and RP1-3 (a). Positively (blue) and (b) negatively (red) charged residues are shown.
Figure 2. The selective interaction between RP1 and the mammalian and bacterial membrane models. Two representative snapshots showing the interaction of RP1 with (a) the POPC and (b) the POPC (blue)/POPG (red) membrane models. RP1 and phosphorous atoms are shown in van der Waals representation.
Figure 3. RP1 mass density profiles. Mass density profiles calculated in three representative windows, (a) 0–20 ns, (b) 140–160 ns, and (c) 280–300 ns, for the MD simulations of RP1 in POPC (top) and in POPC/POPG (bottom) membrane models.
Figure 4. Preferential interaction of the positively charged Lys residues of RP1-3 with the negatively charged POPG heads. Snapshot showing the membrane defect formed in the POPC/POPG simulation. (a) The interaction between Lys residues and the phosphate groups of the POPG lipids (P atoms are shown in van der Waals representation). (b) Radial distribution function showing the distance (Å) between the Lys residues and the phosphorous atoms of POPG (black line) and POPC (red line) lipids (c).
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