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Tigecycline, a protein translation inhibitor, is a treatment of last resort for infections caused by the opportunistic multidrug resistance human pathogen Acinetobacter baumannii. However, strains resistant to tigecycline were reported not long after its clinical introduction. Translation inhibitor antibiotics perturb ribosome function and induce the reduction of (p)ppGpp, an alarmone involved in the stringent response that negatively modulates ribosome production. Through RNA sequencing, this study revealed a significant reduction in the transcription of genes in citric acid cycle and cell respiration, suggesting tigecycline inhibits or slows down bacterial growth. Our results indicated that the drug-induced reduction of (p)ppGpp level promoted the production but diminished the degradation of ribosomes, which mitigates the translational inhibition effect by tigecycline. The reduction of (p)ppGpp also led to a decrease of transcription coupled nucleotide excision repair which likely increases the chances of development of tigecycline resistant mutants. Increased expression of genes linked to horizontal gene transfer were also observed. The most upregulated gene, rtcB, involving in RNA repair, is either a direct tigecycline stress response or is in response to the transcription de-repression of a toxin-antitoxin system. The most down-regulated genes encode two β-lactamases, which is a possible by-product of tigecycline-induced reduction in transcription of genes associated with peptidoglycan biogenesis. This transcriptomics study provides a global genetic view of why A. baumannii is able to rapidly develop tigecycline resistance.
|Number of pages||11|
|Journal||Frontiers in Microbiology|
|Publication status||Published - 27 Oct 2020|
Bibliographical noteCopyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
- Acinetobacter baumannii
- antibiotic resistance
- bacterial physiological response to antibiotics
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- 3 Finished
Stronger Together: Understanding Antibiotic Synergy on a Molecular Level
3/12/18 → 3/12/21
Pacing across the membrane: Characterising the PACE family of multidrug efflux systems
Paulsen, I., Hassan, K. & Henderson, P.
1/01/17 → 31/12/20
Building virtual cyanobacteria: moving beyond the genomics era
Paulsen, I., PhD Contribution (ARC), P. C., PhD Contribution 2 (ARC), P. C. 2., MQRES, M., MQRES 3 (International), M. 3. & MQRES 4 (International), M.
1/12/14 → 30/11/20