Transcriptomics revealed the impact of the translational inhibitor tigecycline on Acinetobacter baumannii

We applied RNA sequencing (RNA-Seq) to define the global changes in A. baumannii gene transcription in response to tigecycline exposure. Tigecycline treatment resulted in increased expression of genes involved in translational initiation, but decreased expression of genes involved in translational elongation, consistent with ribosomal stalling occurring. We also observed a decrease in expression of genes from the TCA cycle, respiration, cell division, and peptidoglycan synthesis, which is consistent with its action as a bacteriostatic antibiotic. Tigecycline exposure also had an unexpected effect on other resistance genes: two ß-lactamases-encoding genes showed significantly reduced transcription, and interestingly, a checkerboard assay showed marginal synergy between tigecycline and ß-lactam antibiotics in inhibiting the growth of A. baumannii. Tigecycline also induced increased expression of genes involved in horizontal gene transfer (HGT) and spontaneous mutation mediated by a DNA mismatch repair enzyme MutS, suggesting tigecycline may lead to increased rates of MDR development during clinical treatments. Overall design: The transcriptomes of tigecycline-treated and non-treated A. baumannii strain (global clonal lineage I) were compared through. The cells were grown to exponential phase, then the culture was splited into two, one with tigecycline treatment at 1/2 MIC and the other without. After this, the cultures were further grew for 30 minutes at 37 degree with shaking, and then the total RNA was extracted. Three biological replicates were prepared, which resulted into 6 total RNA samples.