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| Status |
Public on Nov 09, 2023 |
| Title |
Co-chaperone-mediated post-translational control of efflux pump induction underlies adaptive β-lactam resistance in Caulobacter crescentus [RNA-seq] |
| Organism |
Caulobacter vibrioides |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The acquisition of multi-drug resistance (MDR) determinants jeopardizes treatment of bacterial infections with antibiotics. The tripartite efflux pump AcrAB-NodT confers adaptive MDR in the non-pathogenic α-proteobacterium Caulobacter crescentus via transcriptional induction by first-generation quinolone antibiotics. We discovered that overexpression of AcrAB-NodT by mutation or exogenous inducers confers resistance to cephalosporin and penicillin (β-lactam) antibiotics. Combining two-step mutagenesis-sequencing (Mut-Seq) and cephalosporin-resistant point mutants, we dissected how TipR targets a common operator of divergent tipR and acrAB-nodT promoter in adaptive and/or potentiated AcrAB-NodT-directed efflux. Chemical screening identified compounds that either interfere with DNA-binding by TipR or induce its ClpXP-dependent proteolytic turnover. We found that long-term induction of AcrAB-NodT disfigures the envelope and that homeostatic control by TipR includes co-induction of the DnaJ-like co-chaperone DjlA, to boost pump assembly and/or capacity in anticipation of envelope stress. Thus, the adaptive MDR regulatory circuitry reconciles drug efflux with co-chaperone function for trans-envelope assemblies and maintenance.
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| |
|
| Overall design |
Global transcriptome profiling (gene expression) by RNA-Seq in Caulobacter crescentus NA1000(WT) after Nalidixic acid treatment.
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| |
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| Contributor(s) |
Costafrolaz J, Panis G, Casu B, Ardissone S, Degeorges L, Pilhofer M, Viollier PH |
| Citation(s) |
38051727 |
| |
| Submission date |
Feb 16, 2023 |
| Last update date |
Jan 03, 2024 |
| Contact name |
Patrick H. Viollier |
| E-mail(s) |
Patrick.Viollier@unige.ch
|
| Organization name |
University of Geneva, Faculty of Medicine / CMU
|
| Department |
Dept. Microbiology and Molecular Medicine
|
| Street address |
Rue Michel Servet 1
|
| City |
Geneva 4 |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL24555 |
Illumina NextSeq 500 (Caulobacter vibrioides) |
|
| Samples (4)
|
| GSM7049363 |
RNA-Seq_Caulobacter_crescentus_NA1000(WT)_rep1 |
| GSM7049364 |
RNA-Seq_Caulobacter_crescentus_NA1000(WT)_rep2 |
| GSM7049365 |
RNA-Seq_Caulobacter_crescentus_NA1000(WT)+Nal_rep1 |
| GSM7049366 |
RNA-Seq_Caulobacter_crescentus_NA1000(WT)+Nal_rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE225489 |
Co-chaperone-mediated post-translational control of efflux pump induction underlies adaptive β-lactam resistance in Caulobacter crescentus |
|
| Relations |
| BioProject |
PRJNA935787 |
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