title: Differential scanning calorimetry of whole Escherichia coli treated with the antimicrobial peptide MSI-78 indicate a multi-hit mechanism with ribosomes as a novel target.
abstract: Differential Scanning Calorimetry (DSC) of intact Escherichia coli (E. coli) was used to identify non-lipidic targets of the antimicrobial peptide (AMP) MSI-78. The DSC thermograms revealed that, in addition to its known lytic properties, MSI-78 also has a striking effect on ribosomes. MSI-78's effect on DSC scans of bacteria was similar to that of kanamycin, an antibiotic drug known to target the 30S small ribosomal subunit. An in vitro transcription/translation assay helped confirm MSI-78's targeting of ribosomes. The scrambled version of MSI-78 also affected the ribosome peak of the DSC scans, but required greater amounts of peptide to cause a similar effect to the unscrambled peptide. Furthermore, the effect of the scrambled peptide was not specific to the ribosomes; other regions of the DSC thermogram were also affected. These results suggest that MSI-78's effects on E. coli are at least somewhat dependent on its particular structural features, rather than a sole function of its overall charge and hydrophobicity. When considered along with earlier work detailing MSI-78's membrane lytic properties, it appears that MSI-78 operates via a multi-hit mechanism with multiple targets.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland , St. John's Newfoundland and Labrador , Canada.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Brannan
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland , St. John's Newfoundland and Labrador , Canada.
authors.forename: William A
authors.initials: WA
authors.lastname: Whelan
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland , St. John's Newfoundland and Labrador , Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: Cole
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland , St. John's Newfoundland and Labrador , Canada ; Department of Physics and Physical Oceanography, Memorial University of Newfoundland , St. John's Newfoundland and Labrador , Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Booth
keywords: Antimicrobial peptides; Differential Scanning Calorimetry (DSC); Membrane active peptides