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| Status |
Public on May 23, 2023 |
| Title |
The response of WT, ∆rip1, and ∆sigL strains of Mycobacterium tuberculosis to dipyridyl treatment |
| Organism |
Mycobacterium tuberculosis H37Rv |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Mycobacterium tuberculosis is exposed to a variety of stresses during a chronic infection, as the immune system simultaneously produces bactericidal compounds and starves the pathogen for essential nutrients. The intramembrane protease, Rip1, plays an important role in the adaptation to these stresses, at least partially by the cleavage of membrane bound transcriptional regulators. Although Rip1 is known to be critical for surviving copper intoxication and nitric oxide exposure, these stresses do not fully account the regulatory protein’s essentiality during infection. In this work, we demonstrate that Rip1 is also necessary for growth in low iron and zinc conditions, similar to those imposed by the immune system. Using a newly generated library of sigma factor mutants, we show that the known regulatory target of Rip1, SigL, shares this defect. Transcriptional profiling under iron limiting conditions supported the coordinated activity of Rip1 and SigL and demonstrated that the loss of these proteins produces an exaggerated iron starvation response. These observations demonstrate that Rip1 coordinates several aspects of metal homeostasis and suggest that a Rip1- and SigL-dependent pathway is involved in the adaptation to the iron deficient environments encountered during infection.
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| |
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| Overall design |
Gene expression profiling of Mycobacterium tuberculosis WT H37Rv and knockout mutants in response to dipryidyl treatment
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| Contributor(s) |
Nelson SJ, Ioerger TR, Sassetti CM |
| Citation(s) |
37318217 |
| |
| Submission date |
Apr 11, 2023 |
| Last update date |
Sep 14, 2023 |
| Contact name |
Christopher Sassetti |
| Organization name |
University of Massachusetts Chan Medical School
|
| Street address |
55 Lake Ave North
|
| City |
Worcester |
| State/province |
MA |
| ZIP/Postal code |
01655 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL29823 |
Illumina HiSeq 4000 (Mycobacterium tuberculosis H37Rv) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA954442 |
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