Tobramycin Stress Induced Differential Gene Expression in Acinetobacter baumannii

Acinetobacter baumannii is a multidrug-resistant bacteria responsible for nosocomial infections with significant fatality rates globally. Therapeutic failure and relapse of infection has been associated with persister cells formation which can also lead to resistance in A. baumannii. In the present study, we observed that A. baumannii ATCC 17978 in exponential phase survived lethal concentrations of amikacin, rifampicin and ciprofloxacin by generating persister cells but was unable to survive tobramycin treatment. The transcriptome of A. baumannii ATCC 17978 was analyzed following exposure to a high concentration of tobramycin (10 x MIC) for a short period of time to study the possible mechanisms responsible for lethality. Tobramycin reduced the expression of genes involved in energy production (nuoH, nuoN, nuoM, cydA, sucC), oxidative stress protection (tauD, cysD), and nutrition uptake (ompW) significantly. In addition, hemerythrin (non-heme di-iron oxygen-binding protein) was found to be the most downregulated gene in response to tobramycin which needs to be further studied for its role in susceptibility to antibiotics. Tobramycin upregulated the expression of genes that are mainly involved in stress response (leucine catabolism, DNA repair and HicAB toxin-antitoxin system). The differentially expressed genes highlighted in the study provided insight into the probable molecular mechanism of tobramycin-induced cell death and revealed some novel targets that can be explored further for their potential to control A. baumannii.

Automated summary

This study analyzed the transcriptome of A. baumannii ATCC 17978 after exposure to high concentration of tobramycin, revealing the potential molecular mechanism of tobramycin-induced cell death and identifying novel targets for further exploration.