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A Truncated AdeS Kinase Protein Generated by ISAba1 Insertion Correlates with Tigecycline Resistance in Acinetobacter baumannii
- Source :
- PLoS ONE, PLoS ONE, Vol 7, Iss 11, p e49534 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Over-expression of AdeABC efflux pump stimulated continuously by the mutated AdeRS two component system has been found to result in antimicrobial resistance, even tigecycline (TGC) resistance, in multidrug-resistant Acinetobacter baumannii (MRAB). Although the insertion sequence, ISAba1, contributes to one of the AdeRS mutations, the detail mechanism remains unclear. In the present study we collected 130 TGC-resistant isolates from 317 carbapenem resistant MRAB (MRAB-C) isolates, and 38 of them were characterized with ISAba1 insertion in the adeS gene. The relationship between the expression of AdeABC efflux pump and TGC resistant was verified indirectly by successfully reducing TGC resistance with NMP, an efflux pump inhibitor. Further analysis showed that the remaining gene following the ISAba1 insertion was still transcribed to generate a truncated AdeS protein by the Pout promoter on ISAba1 instead of frame shift or pre-termination. Through introducing a series of recombinant adeRS constructs into a adeRS knockout strain, we demonstrated the truncated AdeS protein was constitutively produced and stimulating the expression of AdeABC efflux pump via interaction with AdeR. Our findings suggest a mechanism of antimicrobial resistance induced by an aberrant cytoplasmic sensor derived from an insertion element.
- Subjects :
- Acinetobacter baumannii
Bacterial Diseases
Transcription, Genetic
Operon
lcsh:Medicine
Minocycline
Tigecycline
Drug resistance
Gene Order
Molecular Cell Biology
Pathology
Cluster Analysis
Insertion sequence
lcsh:Science
Promoter Regions, Genetic
Multidisciplinary
Protein Kinase Signaling Cascade
biology
Signaling Cascades
Clinical Laboratory Sciences
Anti-Bacterial Agents
Infectious Diseases
Medicine
Efflux
Research Article
Signal Transduction
medicine.drug
Drugs and Devices
Genotype
Molecular Sequence Data
Microbial Sensitivity Tests
Frameshift mutation
Microbiology
Antibiotic resistance
Diagnostic Medicine
Drug Resistance, Bacterial
medicine
Humans
Amino Acid Sequence
Biology
Base Sequence
lcsh:R
Gene Expression Regulation, Bacterial
biology.organism_classification
Molecular biology
Mutagenesis, Insertional
Mutation
DNA Transposable Elements
lcsh:Q
ATP-Binding Cassette Transporters
Infectious Disease Modeling
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....e898fe137eb7e140655ae582b19c541b