New antimicrobial peptides against foodborne pathogens: From in silico design to experimental evidence.
Recently there has been growing interest in the discovery of new antimicrobial agents to increase safety and shelf-life of food products. Here, we developed an innovative approach by introducing the concept that mitochondrial targeting peptides (MTP) can interact and disrupt bacterial membranes, acting as antimicrobial agents. As proof-of-principle, we used a multidisciplinary strategy by combining in silico predictions, docking simulations and antimicrobial assays, to identify two peptides, MTP1 and MTP2, which were structurally and functionally characterized. Both compounds appeared effective against Listeria monocytogenes, one of the most important foodborne pathogens. Specifically, a significant bactericidal activity was evidenced with EC50 values of 16.8±1.2μM for MTP1 and 109±7.0μM for MTP2. Finally, NMR structure determinations suggested that MTP1 would be oriented into the membrane bilayer, while the molecular shape of MTP2 could indicate porin-mediated antimicrobial mechanisms, as predicted using molecular docking analysis. Therefore, MTPs represent alternative sources to design new potential bio-preservatives.
Institute of Biosciences and BioResources (IBBR)-UOS Na, National Research Council (CNR-IBBR), Via Pietro Castellino 111, 80131 Naples, Italy. Electronic address: gianna.palmieri@ibbr.cnr.it.
Gianna
G
Palmieri
Institute of Biosciences and BioResources (IBBR)-UOS Na, National Research Council (CNR-IBBR), Via Pietro Castellino 111, 80131 Naples, Italy.
Marco
M
Balestrieri
Department of Food Microbiology, Istituto Zooprofilattico Sperimentale del Mezzogiorno, via della salute, 2, 80055 Portici, Italy.
Yolande T R
YT
Proroga
Department of Pharmacy, University of Naples Federico II, Via Mezzocannone, 16, 80134 Naples, Italy.
Lucia
L
Falcigno
Institute of Food Science, National Research Council (CNR-ISA), Via Roma 52, 83100 Avellino, Italy.
Angelo
A
Facchiano
Institute of Biosciences and BioResources (IBBR)-UOS Na, National Research Council (CNR-IBBR), Via Pietro Castellino 111, 80131 Naples, Italy.
Alessia
A
Riccio
Department of Food Microbiology, Istituto Zooprofilattico Sperimentale del Mezzogiorno, via della salute, 2, 80055 Portici, Italy.
Federico
F
Capuano
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino 1, 80137 Naples, Italy.
Raffaele
R
Marrone
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino 1, 80137 Naples, Italy.
Gianluca
G
Neglia
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino 1, 80137 Naples, Italy.
Aniello
A
Anastasio
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D005516:Food Microbiology; D006801:Humans; D008089:Listeria monocytogenes / Q000187:drug effects; D062105:Molecular Docking Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D010455:Peptides; C000613483:mitochondrial-targeted peptide 1; C000613484:mitochondrial-targeted peptide 2
Antimicrobial peptide; Food bio-preservatives; Listeria monocytogenes; Mitochondrial-targeted peptide; Structural analysis