title: Species-selective killing of bacteria by antimicrobial peptide-PNAs.
abstract: Broad-spectrum antimicrobials kill indiscriminately, a property that can lead to negative clinical consequences and an increase in the incidence of resistance. Species-specific antimicrobials that could selectively kill pathogenic bacteria without targeting other species in the microbiome could limit these problems. The pathogen genome presents an excellent target for the development of such antimicrobials. In this study we report the design and evaluation of species-selective peptide nucleic acid (PNA) antibacterials. Selective growth inhibition of B. subtilis, E. coli, K. pnuemoniae and S. enterica serovar Typhimurium in axenic or mixed culture could be achieved with PNAs that exploit species differences in the translation initiation region of essential genes. An S. Typhimurium-specific PNA targeting ftsZ resulted in elongated cells that were not observed in E. coli, providing phenotypic evidence of the selectivity of PNA-based antimicrobials. Analysis of the genomes of E. coli and S. Typhimurium gave a conservative estimate of >150 PNA targets that could potentially discriminate between these two closely related species. This work provides a basis for the development of a new class of antimicrobial with a tuneable spectrum of activity.
authors.affiliation: School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Madhav
authors.initials: M
authors.lastname: Mondhe
authors.affiliation: School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Ashley
authors.initials: A
authors.lastname: Chessher
authors.affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, London, United Kingdom.
authors.forename: Shan
authors.initials: S
authors.lastname: Goh
authors.affiliation: School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Liam
authors.initials: L
authors.lastname: Good
authors.affiliation: School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: James E M
authors.initials: JE
authors.lastname: Stach
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001412:Bacillus subtilis; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D004926:Escherichia coli / Q000235:genetics; D007711:Klebsiella pneumoniae; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D020135:Peptide Nucleic Acids / Q000378:metabolism / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000235:genetics; D013045:Species Specificity
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D020135:Peptide Nucleic Acids