Targeting bacterial gyrase with cystobactamid, fluoroquinolone and aminocoumarin antibiotics induces distinct molecular signatures in Pseudomonas aeruginosa

The design of novel antibiotics that break antimicrobial resistance relies on a profound understanding of their mechanism of action. While it has been shown that the cellular effects of antibiotics cluster according to their molecular targets, we investigated whether compounds binding to different sites of the same target can be differentiated by their transcriptome or metabolome signatures. The effects of three fluoroquinolones, two aminocoumarins and two cystobactamids, all inhibiting bacterial gyrase, on Pseudomonas aeruginosa at sub-inhibitory concentrations were captured by RNA sequencing. Overall design: RNASeq of Pseudomonas aeruginosa PA14 treated with gyrase inhibitors from three different classes and untreated control- planctonic growth in BM2 medium.