Differential transcriptome profiling of P. aeruginosa PAO1 with oxythiamine treatment

We report antibacterial potency of oxythiamine, which is a known transketolase inhibitor in eukaryotes. Oxythiamine inhibited the growth of P. aeruginosa PAO1 and clinical isolates in thiamine-depleted medium only. Metabolic and trascriptomic analyses indicated that oxythiamine was converted to oxythiamine pyrophosphate that subsequently inhibited several vitamin B1-dependent enzymes. Furthermore, a system-level perturbation of thiamine metabolism sensitized P. aeruginosa to multiple small-molecules informing the potential development of a rational drug combination. Transcriptomic observation of isolated RNA samples from P. aeruginosa PAO1 with or without oxythiamine treatment for 30 and 180 minutes