Perrone_Front Microbiol_2017.pdf (1.89 MB)
A novel TetR-like transcriptional regulator is induced in acid-nitrosative stress and controls expression of an efflux pump in mycobacteria
journal contribution
posted on 2023-06-09, 08:34 authored by Filomena Perrone, Barbara De Siena, Lidia Muscariello, Sharon L Kendall, Simon WaddellSimon Waddell, Margherita SaccoMycobacterium tuberculosis has the ability to survive inside macrophages under acid-nitrosative stress. M. tuberculosis Rv1685c and its ortholog in M. smegmatis, MSMEG_3765, are induced on exposure to acid-nitrosative stress. Both genes are annotated as TetR transcriptional regulators, a family of proteins that regulate a wide range of cellular activities, including multidrug resistance, carbon catabolism and virulence. Here, we demonstrate that MSMEG_3765 is co-transcribed with the upstream genes MSMEG_3762 and MSMEG_3763, encoding efflux pump components. RTq-PCR and GFP-reporter assays showed that the MSMEG_3762/63/65 gene cluster, and the orthologous region in M. tuberculosis (Rv1687c/86c/85c), was up-regulated in a MSMEG_3765 null mutant, suggesting that MSMEG_3765 acts as a repressor, typical of this family of regulators. We further defined the MSMEG_3765 regulon using genome-wide transcriptional profiling and used reporter assays to confirm that the MSMEG_3762/63/65 promoter was induced under acid-nitrosative stress. A putative 36 bp regulatory motif was identified upstream of the gene clusters in both M. smegmatis and M. tuberculosis and purified recombinant MSMEG_3765 protein was found to bind to DNA fragments containing this motif from both M. smegmatis and M. tuberculosis upstream regulatory regions. These results suggest that the TetR repressor MSMEG_3765/Rv1685c controls expression of an efflux pump with an, as yet, undefined role in the mycobacterial response to acid-nitrosative stress.
History
Publication status
- Published
File Version
- Published version
Journal
Frontiers in MicrobiologyISSN
1664-302XPublisher
Frontiers MediaExternal DOI
Issue
2039Volume
8Department affiliated with
- BSMS Publications
Research groups affiliated with
- Wellcome Trust Brighton and Sussex Centre for Global Health Research Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-11-02First Open Access (FOA) Date
2017-11-02First Compliant Deposit (FCD) Date
2017-11-02Usage metrics
Categories
No categories selectedLicence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC