title: 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123, Palermo, Italy. domenico.schillaci@unipa.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Schillaci
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123, Palermo, Italy.|IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia, Via Michele Miraglia, 20, 90139, Palermo, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Spinello
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123, Palermo, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cusimano
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123, Palermo, Italy.|IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia, Via Michele Miraglia, 20, 90139, Palermo, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Cascioferro
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123, Palermo, Italy.|IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia, Via Michele Miraglia, 20, 90139, Palermo, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Barone
authors.affiliation: Istituto Zooprofilattico Sperimentale della Sicilia, A. Mirri. Via Marinuzzi 3, 90129, Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Vitale
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Via Archirafi, 32, 90123, Palermo, Italy.|IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia, Via Michele Miraglia, 20, 90139, Palermo, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arizza
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013947:Thymosin / Q000737:chemistry / Q000235:genetics*; D000099201:Thymosin beta(4)
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: Antimicrobial peptides; Molecular dynamics; Staphylococcal biofilms; Thymosin