The Transcriptomic Signature of Tigecycline in Acinetobacter baumannii

Frontiers in Microbiology
Liping LiIan T Paulsen

Abstract

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 stre...Continue Reading

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Datasets Mentioned

BETA
GSE131451
AB0057
EDGE-pro

Methods Mentioned

BETA
RNA-Seq
aminoacylation

Software Mentioned

DEseq R package
Biocyc
TMHMM Server
- pro ( Expression Prokaryotic Genomes
EDGE

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