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Mar Drugs
2019 Mar 08;173:. doi: 10.3390/md17030159.
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A Synthetic Derivative of Antimicrobial Peptide Holothuroidin 2 from Mediterranean Sea Cucumber (Holothuria tubulosa) in the Control of Listeria monocytogenes.
Cusimano MG
,
Spinello A
,
Barone G
,
Schillaci D
,
Cascioferro S
,
Magistrato A
,
Parrino B
,
Arizza V
,
Vitale M
.
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Due to the limited number of available antibiotics, antimicrobial peptides (AMPs) are considered antimicrobial candidates to fight difficult-to-treat infections such as those associated with biofilms. Marine environments are precious sources of AMPs, as shown by the recent discovery of antibiofilm properties of Holothuroidin 2 (H2), an AMP produced by the Mediterranean sea cucumber Holothuria tubulosa. In this study, we considered the properties of a new H2 derivative, named H2d, and we tested it against seven strains of the dangerous foodborne pathogen Listeria monocytogenes. This peptide was more active than H2 in inhibiting the growth of planktonic L. monocytogenes and was able to interfere with biofilm formation at sub-minimum inhibitory concentrations (MICs). Atomic-level molecular dynamics (MD) simulations revealed insights related to the enhanced inhibitory activity of H2d, showing that the peptide is characterized by a more defined tertiary structure with respect to its ancestor. This allows the peptide to better exhibit an amphipathic character, which is an essential requirement for the interaction with cell membranes, similarly to other AMPs. Altogether, these results support the potential use of our synthetic peptide, H2d, as a template for the development of novel AMP-based drugs able to fight foodborne that are resistant to conventional antibiotics.
Figure 1. (a) Structure of the most representative cluster of H2, Tag, and H2d obtained from the molecular dynamics (MD) simulations; blue and red colors respectively identify the H2 and Tag moieties in H2d. (b) Ramachandran plots showing the values of the psi and phi angles assumed by each residue. (c) Electrostatic potential of the peptides structures, shown as surfaces; red and blue colors are used for negative and positive values, respectively.
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