Mechanism of escherichia coli resistance to pyrrhocoricin

Shalini Narayanan, Joyanta K. Modak, Catherine S. Ryan, Jose Garcia-Bustos, John K. Davies, Anna Roujeinikova

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2754-2762
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume58
Issue number5
DOIs
Publication statusPublished - May 2014

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