Activity of rx-04 pyrrolocytosine protein synthesis inhibitors against multidrug-resistant gram-negative bacteria

Anna Vickers, Shazad Mushtaq, Neil Woodford, Michel Doumith, David Livermore

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Pyrrolocytosines RX-04A to -D are designed to bind to the bacterial 50S ribosomal subunit differently from currently used antibiotics. The four analogs had broad anti-Gram-negative activity: RX-04A—the most active analog—inhibited 94.7% of clinical Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa at 0.5 to 4 g/ml, with no MICs of 8 g/ml. MICs for multidrug-resistant (MDR) carbapenemase producers were up to 2-fold higher than those for control strains; values were highest for one Serratia isolate with porin and efflux lesions. mcr-1 did not affect MICs.

Original languageEnglish
Article numbere00689-18
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number8
DOIs
Publication statusPublished - Aug 2018

Keywords

  • 50S ribosomal subunit
  • Blasticidin
  • Mcr-1
  • Pyrrolocytosine

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