A peptide from human β thymosin as a platform for the development of new anti-biofilm agents for Staphylococcus spp. and Pseudomonas aeruginosa

Abstract

Conventional antibiotics might fail in the treatment of biofilm-associated infections causing infection recurrence and chronicity. The search for antimicrobial peptides has been performed with the aim to discover novel anti-infective agents active on pathogens in both planktonic and biofilm associated forms. The fragment 9-19 of human thymosin β4 was studied through 1 μs MD simulation. Two main conformations of the peptide were detected, both constituted by a central hydrophobic core and by the presence of peripheral charged residues suggesting a possible mechanism of interaction with two models of biological membranes, related to eukaryotic or bacterial membrane respectively. In addition, the peptide was chemically synthesized and its antimicrobial activity was tested in vitro against planktonic and biofilm form of a group of reference strains of Staphylococcus spp. and one P. aeruginosa strain. The human thymosin β4 fragment EIEKFDKSKLK showed antibacterial activity against staphylococcal strains and Pseudomonas aeruginosa ATCC 15442 at concentrations from 12.5 to 6.2 mg/ml and inhibited biofilm formation at sub-inhibitory concentrations (3.1-0.75 mg/ml). The activity of the fragment in inhibiting biofilm formation, could be due to the conformations highlighted by the MD simulations, suggesting its interaction with the bacterial membrane. Human thymosin β4 fragment can be considered a promising lead compound to develop novel synthetic or recombinant derivatives with improved pharmaceutical potential.

Control of Growth and Persistence of Listeria monocytogenes and β-Lactam-Resistant Escherichia coli by Thymol in Food Processing Settings

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New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

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A Synthetic Derivative of Antimicrobial Peptide Holothuroidin 2 from Mediterranean Sea Cucumber (Holothuria tubulosa) in the Control of Listeria monocytogenes

“…The lowest energy model was taken as a starting point for subsequent simulations, as seen in Figure 1a. In particular, the stability of the peptide conformations in physiological conditions was assessed by MD simulations, following reported procedures [44,45]. MD simulations were performed using a Particle Mesh Ewald MD (PMEMD) module of Amber18 [46], using the Amber99SB-ILDN force field [47].…”