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. 2018 Jul 27;62(8):e00689-18.
doi: 10.1128/AAC.00689-18. Print 2018 Aug.

Activity of RX-04 Pyrrolocytosine Protein Synthesis Inhibitors against Multidrug-Resistant Gram-Negative Bacteria

Anna Vickers  1 , Shazad Mushtaq  1 , Neil Woodford  1 , Michel Doumith  1 , David M Livermore  2   3
Affiliations

Activity of RX-04 Pyrrolocytosine Protein Synthesis Inhibitors against Multidrug-Resistant Gram-Negative Bacteria

Anna Vickers et al. Antimicrob Agents Chemother. .

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 μg/ml, with no MICs of >8 μg/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.

Keywords: 50S ribosomal subunit; blasticidin; mcr-1; pyrrolocytosine.

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FIG 1
FIG 1
RX-04 pyrrolocytosine structures.
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