title: Mechanism of Escherichia coli resistance to Pyrrhocoricin.
abstract: Due to their lack of toxicity to mammalian cells and good serum stability, proline-rich antimicrobial peptides (PR-AMPs) have been proposed as promising candidates for the treatment of infections caused by antimicrobial-resistant bacterial pathogens. It has been hypothesized that these peptides act on multiple targets within bacterial cells, and therefore the likelihood of the emergence of resistance was considered to be low. Here, we show that spontaneous Escherichia coli mutants resistant to pyrrhocoricin arise at a frequency of approximately 6 × 10(-7). Multiple independently derived mutants all contained a deletion in a nonessential gene that encodes the putative peptide uptake permease SbmA. Sensitivity could be restored to the mutants by complementation with an intact copy of the sbmA gene. These findings question the viability of the development of insect PR-AMPs as antimicrobials.
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Shalini
authors.initials: S
authors.lastname: Narayanan
authors.forename: Joyanta K
authors.initials: JK
authors.lastname: Modak
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Ryan
authors.forename: Jose
authors.initials: J
authors.lastname: Garcia-Bustos
authors.forename: John K
authors.initials: JK
authors.lastname: Davies
authors.forename: Anna
authors.initials: A
authors.lastname: Roujeinikova
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D019476:Insect Proteins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D019476:Insect Proteins; C087710:pyrrhocoricin protein, Pyrrhocoris apterus