Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Transcriptomic Signature of Tigecycline in Acinetobacter baumannii

ABSTRACT: Tigecycline, a protein translation inhibitor, is a treatment of last resort for infections caused by the opportunistic multidrug resistant 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 b-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.

ORGANISM(S): Acinetobacter baumannii

PROVIDER: GSE131451 | GEO | 2020/08/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

ppGpp signal plays critical role in pathogenesis of Acinetobacter baumannii 17978

Project description:Acinetobacter baumannii is a major cause of nosocomial infections which can survive in different hospital environments and its multidrug-resistant capacity is major concern now-a-days. ppGpp dependent stringent response mediates reprogramming of gene expression with diverse function in many bacteria. A baumannii A1S_0579 gene is responsible for ppGpp production. Transcriptome analysis of early stationary phase cultures represents several differentially expressed genes in ppGpp deficient strain (∆A1S_0579). We found that the expression of csu operon, which is important in pili biosynthesis for early biofilm formation, was significantly reduced in the ppGpp-deficient strain. Our findings showed that ppGpp signaling plays critical role in biofilm formation, surface motility, adherence and virulence of A baumannii. This study is the first demonstration of the association between ppGpp and pathogenicity of A. baumannii.

2021-05-01 | GSE173627 | GEO

iTRAQ based proteomic analysis to reveal the mechanism of tigecycline resistance in Acinetobacter baumannii

Project description:The antibiotic resistance of A. baumannii has been increasing in recent years. There are still many questions unclear concerning the mechanism of tigecycline resistance in A. baumannii. iTRAQ based proteomic analysis were used to reveal the mechanism of tigecycline resistance in Acinetobacter baumannii.

2023-07-20 | PXD034784 | Pride

Project description:tigecycline resistant Acinetobacter baumannii in China

| PRJNA577511 | ENA

Novel physiological traits modulated by light in Acinetobacter baumannii assessed by whole transcriptome analysis.

Project description:We have shown recently that in the human pathogen Acinetobacter baumannii, light is able to modulate key aspects contributing to its success as a pathogen such as motility, biofilm formation and virulence in a way that depends on the BLUF photoreceptor BlsA at 24ºC. In addition, light can induce reduction in susceptibility to certain antibiotics such as minocycline and tigecycline in a photoreceptor-independent manner, directly inducing expression of resistance genes. In this work, we performed RNAseq studies to identify new traits modulated by light in this pathogen in A. baumannii strain ATCC 19606. We have found 226 differentially expressed genes between light and dark, which comprise not only important determinants related to pathogenicity/resistance, but also to the bacteria´s survival in the environment.

2017-03-21 | GSE90630 | GEO

Acinetobacter baumannii

Project description:Genomic sequencing of tigecycline-resistant Acinetobacter baumannii

| PRJNA270778 | ENA

The stringent response inhibits DNA replication initiation in E. coli by modulating supercoiling of oriC

Project description:The stringent response enables bacteria to respond to a variety of environmental stresses, especially various forms of nutrient limitation. During the stringent response the cell produces large quantities of the nucleotide alarmone ppGpp, which modulates many aspects of cell physiology, including reprogramming transcription, blocking protein translation, and inhibiting new rounds of DNA replication. The mechanism by which ppGpp inhibits DNA replication initiation in Escherichia coli remains unclear. Prior work suggested that ppGpp blocks new rounds of DNA replication by inhibiting transcription of the essential initiation factor dnaA, but we found that replication is still inhibited by ppGpp in cells ectopically producing DnaA. Instead, we provide evidence that a global reduction of transcription by ppGpp prevents replication initiation by modulating the supercoiling state of the origin of replication, oriC. Active transcription normally introduces negative supercoils into oriC to help promote replication initiation, so the accumulation of ppGpp reduces initiation potential at oriC. We find that maintaining transcription near oriC, either by expressing a ppGpp-blind RNA polymerase mutant or by inducing transcription from a ppGpp-insensitive promoter, can strongly bypass the inhibition of replication by ppGpp. Additionally, we show that increasing global negative supercoiling by inhibiting topoisomerase I or by deleting the nucleoid-associated protein seqA, also relieves inhibition. We propose a model, potentially conserved across proteobacteria, in which ppGpp indirectly creates an unfavorable energy landscape for initiation by preventing the introduction of negative supercoils into oriC.

2019-06-11 | GSE128606 | GEO

RNAseq transcriptome analysis of K. pneumoniae MS6671 and E. coli MS8345 treated with PBT2

Project description:The emergence of colistin resistance in carbapenem-resistant and extended-spectrum ß-lactamase (ESBL)-producing bacteria is a significant threat to human health, and new treatment strategies are urgently required. Here we investigated the ability of the safe-for-human use ionophore PBT2 to restore antibiotic sensitivity in several polymyxin-resistant, ESBL-producing, carbapenem resistant Gram-negative human pathogens. PBT2 was observed to resensitize Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including a ‘next generation’ polymyxin derivative, FADDI-287. To gain additional insight into the potential mechanism of action of PBT2, we analyzed the transcriptome of K. pneumoniae and E. coli in the presence of sub-inhibitory concentrations of PBT2. Treatment with PBT2 was associated with multiple stress responses in both K. pneumoniae and E. coli. Significant changes in the transcription of transition metal ion homeostasis genes were observed in both strains.

2019-06-13 | GSE132637 | GEO

The mechanism of tigecycline resistance in Acinetobacter baumannii under sub-minimal inhibitory concentration tigecycline

Project description:The mechanism of tigecycline resistance in Acinetobacter baumannii under sub-minimal inhibitory concentration tigecycline by comparative protemics

2024-01-26 | PXD048947 | iProX

Identification of a novel LysR family transcriptional regulator controlling acquisition of sulfur sources in Acinetobacter baumannii.

Project description:RNA sequencing transcriptomics was performed on a highly multidrug resistant A. baumannii strain belonging to international clone I, AB5075_UW and a transposon insertion inactivated mutant of ABUW_1016 (cbl), which encodes a LysR-type transcriptional regulator.Transcriptomics suggests that Cbl controls expression of the genes involved in acquisition and reduction of various sulfur sources in A. baumannii.

2022-12-15 | GSE183337 | GEO

Transcriptional profiling by array of yeast to identify genes inhibiting mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia

Project description:Haplo-insufficiency profiling followed by Gene-set enrichment analysis of sensitive strains was conducted in yeast treated with tigecycline. This revealed significant enrichment of genes involved in mitochondrial translation, similar to that seen with the known mitochondrial translation inhibitors chloramphenicol and linezolid

2011-11-01 | E-MTAB-814 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data