title: Improved antimicrobial activities of synthetic-hybrid bacteriocins designed from enterocin E50-52 and pediocin PA-1.
abstract: Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics.
authors.affiliation: Department of Genetics, Maharshi Dayanand University, Rohtak, Haryana, India School of Environmental and Biological Sciences, Rutgers State University, New Brunswick, New Jersey, USA.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Tiwari
authors.affiliation: School of Environmental and Biological Sciences, Rutgers State University, New Brunswick, New Jersey, USA.
authors.forename: Katia
authors.initials: K
authors.lastname: Sutyak Noll
authors.affiliation: Department of Biochemistry and Microbiology, Rutgers State University, New Brunswick, New Jersey, USA.
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Cavera
authors.affiliation: School of Environmental and Biological Sciences, Rutgers State University, New Brunswick, New Jersey, USA tchikindas@aesop.rutgers.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Chikindas
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001430:Bacteriocins / Q000737:chemistry* / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000494:pharmacology; D019453:Escherichia coli O157 / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D016982:Micrococcus luteus / Q000187:drug effects; D000070017:Pediocins; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D012477:Salmonella enteritidis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D001952:Bridged-Ring Compounds; D000070017:Pediocins; D011993:Recombinant Fusion Proteins; C074288:pediocin PA-1; C012306:enterocin