title: Sensitization of microcin J25-resistant strains by a membrane-permeabilizing peptide.
abstract: Microcin J25 (MccJ25) is a plasmid-encoded, 21-amino-acid, antibacterial peptide produced by Escherichia coli. MccJ25 inhibits RNA polymerase and the membrane respiratory chain. MccJ25 uptake into E. coli-sensitive strains is mediated by the outer membrane receptor FhuA and the inner membrane proteins TonB, ExbB, ExbD, and SbmA. This peptide is active on some E. coli, Salmonella, and Shigella species strains, while other Gram-negative bacteria, such as clinical isolates of Enterobacter cloacae, Citrobacter freundii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Moraxella catarrhalis, and Salmonella enterica serovar Typhimurium, are completely resistant. In the present work, we demonstrated that the membrane-permeabilizing peptide (KFF)₃K made some resistant strains sensitive to MccJ25, among them S. Typhimurium, where the antibiotic inhibits in vitro cell growth and bacterial replication within macrophages. The results demonstrate that the membrane permeabilization induced by (KFF)₃K allows MccJ25 penetration in an FhuA and SbmA-independent manner and suggest that the combination of both peptides could be considered as a therapeutic agent against pathogenic Salmonella strains.
authors.affiliation: Departamento de Bioquímica de la Nutrición, INSIBIO, Chacabuco 461, 4000 San Miguel de Tucumán, Argentina.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Pomares
authors.forename: Mónica A
authors.initials: MA
authors.lastname: Delgado
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Corbalán
authors.forename: Ricardo N
authors.initials: RN
authors.lastname: Farías
authors.forename: Paula A
authors.initials: PA
authors.lastname: Vincent
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D001430:Bacteriocins / Q000378:metabolism* / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D015169:Colony Count, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; C020411:microcin; D010100:Oxygen
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